Methods and apparatuses for skin treatment using non-thermal tissue ablation

ABSTRACT

Disclosed herein are methods, apparatuses, and devices for treating skin, such as skin tightening or for treating diseases, disorders, and conditions that would benefit from tissue area or volume reduction, skin restoration, skin tightening, skin lifting, or skin repositioning. Such methods and devices include an ablative apparatus, a removal apparatus, and/or a positioning apparatus.

BACKGROUND OF THE INVENTION

This invention relates to methods, apparatuses, and devices for treatingskin and proximal tissue layers (e.g., such as fat, muscle, and facialSMAS (superficial muscular aponeurotic system)), such as skintightening, or for treating diseases, disorders, and conditions thatwould benefit from tissue area or volume reduction, skin restoration,skin tightening, skin lifting, or skin repositioning, or tattoo removal.

Many human health issues arise from the damage or loss of tissue due todisease, advanced age, and/or injury. In aesthetic medicine, eliminationof excess tissue and/or skin laxity is an important concern that affectsmore than 25% of the U.S. population. Conventional surgical therapies(e.g., a face lift, brow lift, or breast lift) can be effective but areoften invasive, inconvenient, and expensive, while scarring limits theapplicability of surgery to certain treatment sites.

Although minimally invasive methods are available, such methods aregenerally less effective than surgical methods. Methods using energysources (e.g., laser, non-coherent light, radiofrequency, or ultrasound)can be effective at improving the architecture and the texture of theskin but are much less effective at tightening the skin or reducing skinlaxity. Neurotoxins, such as botulinum toxin, reduce the formation ofdynamic wrinkles by paralysis of the injected muscles, but such toxinshave minimal or no direct effect on skin tightness or laxity. Finally,dermal fillers, such as hyaluronic acid, are injected in the dermallayer to smooth out wrinkles and improve contours, but such fillers donot directly tighten or reduce laxity of the skin. Thus, surgicaltherapies remain the gold standard for lifting and/or tightening skin,as compared to energy-based techniques (e.g., with laser,radiofrequency, or ultrasound ablation) and injection-based techniques(e.g., with botulinum toxin or hyaluronic acid- or collagen-basedfillers).

Accordingly, there is a need for improved methods and devices thatincrease the effectiveness of minimally-invasive techniques whilemaintaining convenience, affordability, and/or accessibility to patientsdesiring tissue restoration.

SUMMARY OF THE INVENTION

This invention relates to methods and devices using non-thermal tissueablation. The invention features an ablative apparatus for non-thermaltissue ablation including a skin-penetrating component configured toprovide an ablated tissue portion having a width to depth ratio ofbetween about 1:0.3 to about 1:75.

The invention also features a method of treating skin including: (a)positioning the skin using a compressive or a stretching force appliedacross said skin; (b) forming a plurality of ablated tissue portions;and (c) removing the plurality of ablated tissue portions, therebytreating the skin. In a preferred embodiment, the positioning isaccomplished using a compressive force. In some embodiments, the ablatedtissue portions have a width to depth ratio of between about 1:0.3 toabout 1:75. The compressive force applied across the skin compresses theskin in a direction orthogonal to Langer lines. The plurality of ablatedtissue portions is removed using needles with 21G. The plurality ofablated tissue portions being removed is about 10% of the skin within atreatment area.

The invention features a method of treating skin including: (a) forminga plurality of ablated tissue portions having a width to depth ratio ofbetween about 1:0.3 to about 1:1 or of between about 1:25 to about 1:75;and (b) removing the plurality of ablated tissue portions, therebytreating said skin.

The invention features a method of treating skin including: (a) forminga plurality of ablated tissue portions having a change in width as afunction of depth, where the change in width is of between about 10 μmto about 1000 μm (e.g., about 100 μm to about 500 μm or any rangesdescribed herein) as a function of depth; and (b) removing the pluralityof ablated tissue portions, thereby treating the skin.

The invention features a method of treating skin including: (a) forminga plurality of ablated tissue portions including a serrated or scallopedcross-sectional dimension (e.g., in the x-, y-, and/or z-axis); and (b)removing the plurality of ablated tissue portions, thereby treating theskin.

In any of the methods herein, step (b) includes pulling, squeezing,resorbing, desiccating, and/or liquefying the plurality of ablatedtissue portions (e.g., using any method or apparatus described herein).

In any of the methods herein, the method further includes (c)positioning the skin prior to step (a) and/or (b) (e.g., using anymethod or apparatus described herein) using a compressive force appliedacross said skin. In any of the methods herein, step (a) is performedwith an ablative apparatus (e.g., any described herein) and/or step (b)is performed with a removal apparatus (e.g., any described herein)and/or step (c) is performed with a positioning apparatus (e.g., anydescribed herein).

The invention features a positioning apparatus for positioning skinincluding a vacuum tube having at least one dimension of about 0.5 mm ormore (e.g., at least about 1 mm) and a vacuum source, where the vacuumtube is configurably attached to the source and exerts a compressiveforce.

The invention features a positioning apparatus for positioning skinincluding a substrate having at least one dimension of about 0.5 mm ormore (e.g., at least about 1 mm) and a cryosource, where the substrateis configurably attached to the cryosource and provides acryotemperature of about 0 degrees C. or lower (e.g., where theoperating temperature is between 0° C. to −180° C., such as about 0° C.to −20° C.).

The invention features a positioning apparatus for positioning skinincluding an adhesive layer having at least one dimension of about 0.5mm or more (e.g., at least about 1 mm) and exerting a compressive force.In some embodiments, the adhesive layer may alternatively be used tohold the skin in an xy dimension or lift the skin in addition tocompression.

The invention also features an ablative apparatus for non-thermal tissueablation including a skin-penetrating component configured to provide anablated tissue portion having a change in width as a function of depth,where the change in width is of between about 1 μm to about 1000 μm(e.g., about 100 μm to about 500 μm) as a function of depth.

The invention also features an ablative apparatus for non-thermal tissueablation including a skin-penetrating component configured to provide anablated tissue portion including a serrated or scalloped cross-sectionaldimension.

The invention features an ablative apparatus for non-thermal tissueablation including: (a) a skin-penetrating component including a drillbit including one or more spiral channels, a microauger including aspiral flange, a hollow drill bit, a tube including cutting teeth,and/or a spoon bit; and (b) a motor configured to rotate the component,where the motor is configurably attached to the component. In someembodiments, the component rotates from about 50 rpm to about 2500 rpm,such as ranges described herein.

The invention features an ablative apparatus for non-thermal tissueablation including: (a) a skin-penetrating component including a wireand/or a fiber having a first attachment point and a second attachmentpoint; (b) an axle having a sharpened distal end, a center portion, anda proximal end, where the first attachment point of the component isconfigurably attached to the distal end of the axle; and (c) a motorconfigured to rotate the component, where the motor is configurablyattached to the proximal end of the axle. In some embodiments, theskin-penetrating component further includes a second attachment pointand the second attachment point of the component is configurablyattached to the center portion of the axle. In other embodiments, thecomponent rotates from about 500 rpm to about 5000 rpm, such as anyranges described herein.

The invention features an ablative apparatus for non-thermal tissueablation including a skin-penetrating component including a plurality ofcylindrical blades or a plurality of straight blades assembled in afractional pattern. In some embodiments, at least one of the pluralityof cylindrical blades is configurably attached to an actuator forpushing the blade into the skin. In other embodiments, the actuator is avibrating mechanism.

The invention features an ablative apparatus for non-thermal tissueablation including (a) a skin-penetrating component including a highpressure fluid jet; (b) an in-flow tube configured to deliver one ormore fluids to be emitted from the fluid jet; and (c) an optionalout-flow tube configured to collect the one or more fluids after beingemitted from the fluid jet. In some embodiments, the pressure of thehigh pressure fluid jet is from about 1000 psi to about 100000 psi,including other ranges described herein.

The invention features an ablative apparatus for non-thermal tissueablation including (a) a skin-penetrating component including aplurality of cryoprobes and/or a plurality of cryoneedles; (b) acryosource, where each cryoprobe and/or cryoneedle is configurablyattached to the cryosource to provide cryotemperature treatment to skin;and (c) an optional insulator portion to shield regions of non-treatedskin from exposure to the cryotemperature treatment, where the insulatorportion is configurably attached to the component.

The invention features an ablative apparatus for non-thermal tissueablation including (a) a skin-penetrating component including aplurality of needles, where each needle includes a plurality of holesconfigured to deliver one or more chemical or bioactive agents to skin;and (b) a depot including the one or more chemical or bioactive agents(e.g., any described herein), where each needle is configurably attachedto the depot for delivering the one or more chemical or bioactiveagents.

The invention features an ablative apparatus for non-thermal tissueablation including (a) a skin-penetrating component including aplurality of microelectrodes, where each microelectrode includes anactive electrode and a return electrode, or including a femtosecondlaser (e.g., any described herein); (b) a generator configurablyattached to each of the microelectrodes or laser; and (c) an optionalelectrical insulator portion to shield regions of non-treated skin fromexposure to electrical and/or thermal energy, where the electricalinsulator portion is configurably attached to the component. In someembodiments, the laser is an excimer laser (e.g., any described herein).

The invention features an ablative apparatus for non-thermal tissueablation including (a) a skin-penetrating component including aplurality of needles, where each needle includes a plurality of holesconfigured to deliver vacuum to skin; and (b) a vacuum source, whereeach needle is configurably attached to the source. In some embodiments,the vacuum source includes an absolute pressure less than about 6.3 kPa(e.g., from about 0.1 kPa to about 6 kPa, such as from 0.1 kPa to 5 kPa,0.1 kPa to 4 kPa, 0.1 kPa to 3 kPa, 0.1 kPa to 2 kPa, 0.1 kPa to 1 kPa,0.5 kPa to 6 kPa, 0.5 kPa to 5 kPa, 0.5 kPa to 4 kPa, 0.5 kPa to 3 kPa,0.5 kPa to 2 kPa, 0.5 kPa to 1 kPa, 1 kPa to 6 kPa, 1 kPa to 5 kPa, 1kPa to 4 kPa, 1 kPa to 3 kPa, 1 kPa to 2 kPa, 1.5 kPa to 6 kPa, 1.5 kPato 5 kPa, 1.5 kPa to 4 kPa, 1.5 kPa to 3 kPa, or 1.5 kPa to 2 kPa).

In any of the ablative apparatus herein, the apparatus is configured toprovide from about 10 to about 10000 ablated tissue portions per cm²area of the skin region (e.g., including from about 100 to 10000 ablatedtissue portions per cm² area of the skin region, as well as any otherranges described herein). In any of the ablative apparatus herein, theskin-penetrating component includes a drill, a microauger, a tubeincluding cutting teeth, a spoon bit, a wire, a fiber, a blade, ahigh-pressure fluid jet, a cryoprobe, a cryoneedle, a multi-hole needleincluding one or more chemical or bioactive agents, a microelectrode,and/or a vacuum. In any of the ablative apparatus herein, the apparatusfurther includes one or more components selected from the groupconsisting of a motor, an axle, an adjustable depth stop, an in-flowtube, a return electrode, a generator, and an electrical insulator. Insome embodiments, the ablative apparatus further includes a plurality ofthe skin-penetrating components in an array (e.g., in an patterndescribed herein).

In some embodiments, the ablative apparatus of the invention may be usedto treat one or more diseases, disorders, or conditions in underlyingskin layers, such as fat, muscle, and facial SMAS (superficial muscularaponeurotic system). In such embodiments, the ablative apparatus of theinvention may include a skin-penetrating component configured to providean ablated tissue portion having an appropriate depth (e.g., 2-10 mm) toreach the targeted underlying skin layers (e.g., fat, muscle, and facialSMAS).

In some embodiments, the ablative apparatus of the invention removes aplurality of ablated tissue portions using needles with 21G. Theplurality of ablated tissue portions being removed is about 10% of theskin within a treatment area.

The invention also features a removal apparatus for removing one or moreablated tissue portion(s) including: (a) a substrate including aplurality of holes; and (b) a vacuum source, where the substrate isconfigurably attached to the source to deliver vacuum through each holeand to each of the one or more ablated tissue portion(s).

The invention features a removal apparatus for removing one or moreablated tissue portion(s) including an adhesive layer (e.g., anydescribed herein) or an array of probes configured to contact each ofthe one or more ablated tissue portion(s).

The invention features a removal apparatus for removing one or moreablated tissue portion(s) including (a) a plurality of needlesconfigured to contact each of the one or more ablated tissue portion(s);and (b) a heat source configured to deliver heat through the lumen ofeach needle and to each of the one or more ablated tissue portion(s). Insome embodiments, the heat source is selected from a laser source, a hotneedle, radiofrequency, ultrasound, a heated gas, or a heated liquid.

The invention features a removal apparatus for removing one or moreablated tissue portion(s) including (a) a wire having a first attachmentpoint and a second attachment point; (b) an axle having a sharpeneddistal end, a center portion, and a proximal end, where the firstattachment point of the wire is configurably attached to the distal endof the axle and the second attachment point of the wire is configurablyattached to the center portion of the axle, and where the axle isconfigured to contact each of the one or more ablated tissue portion(s);(c) a motor configured to rotate the wire, where the motor isconfigurably attached to the proximal end of the axle; (d) a vacuumsource, and (e) a substrate including a plurality of holes, where thesubstrate is configurably attached to a vacuum source to deliver vacuumthrough each hole and to each of the one or more ablated tissueportion(s).

In any of the distances provided for the removal and/or positioningapparatus, the minimum distance corresponds to the minimal size of theskin-penetrating component of the ablation apparatus. In otherembodiments, the minimum distance corresponds to the minimal size of thearray of a plurality of skin-penetrating components. Exemplary distancesinclude more than about 0.5 mm or between about 0.2 mm to about 20 mm(e.g., from 0.2 mm to 1 mm, 0.2 mm to 2 mm, 0.2 mm to 5 mm, 0.2 mm to 10mm, 0.2 mm to 15 mm, 0.5 mm to 1 mm, 0.5 mm to 2 mm, 0.5 mm to 5 mm, 0.5mm to 10 mm, 0.5 mm to 15 mm, 0.5 mm to 20 mm, 0.75 mm to 1 mm, 0.75 mmto 2 mm, 0.75 mm to 5 mm, 0.75 mm to 10 mm, 0.75 mm to 15 mm, 0.75 mm to20 mm, 1 mm to 1 mm, 1 mm to 2 mm, 1 mm to 5 mm, 1 mm to 10 mm, 1 mm to15 mm, 1 mm to 20 mm, 1.5 mm to 1 mm, 1.5 mm to 2 mm, 1.5 mm to 5 mm,1.5 mm to 10 mm, 1.5 mm to 15 mm, 1.5 mm to 20 mm, 2 mm to 1 mm, 2 mm to2 mm, 2 mm to 5 mm, 2 mm to 10 mm, 2 mm to 15 mm, 2 mm to 20 mm, 2.5 mmto 1 mm, 2.5 mm to 2 mm, 2.5 mm to 5 mm, 2.5 mm to 10 mm, 2.5 mm to 15mm, or 2.5 mm to 20 mm).

The invention also features a device including (a) an ablative apparatusfor non-thermal tissue ablation of any described herein and (b) aremoval apparatus for removing one or more ablated tissue portion(s) ofany described herein, where the removal apparatus is configured toremove one or more ablated tissue portion(s) ablated with the ablativeapparatus.

In some embodiments, the device includes an ablative apparatus includinga drill and a removal apparatus including a vacuum, an ablativeapparatus including a drill and a removal apparatus including anadhesive, an ablative apparatus including a drill (e.g., a hollow drill)and a removal apparatus including a laser, an ablative apparatusincluding a fiber and a removal apparatus including a vacuum, anablative apparatus including a fiber and a removal apparatus includingan adhesive, an ablative apparatus including one or more blades and aremoval apparatus including a vacuum, an ablative apparatus includingone or more blades and a removal apparatus including an adhesive, or anablative apparatus including one or more blades and a removal apparatusincluding a laser, such as any described herein.

In some embodiments, the device further includes a positioning apparatusfor positioning skin (e.g., any described herein), where the positioningapparatus is configured to position skin prior to ablation with theablative apparatus and/or prior to removal with the removal apparatus.In other embodiments, the device further includes one or more sensors todetect position, temperature, skin proximity, microcontours, ablations,skin contact, and/or changes in inductive coupling.

The invention also features a kit including (a) an ablative apparatusfor non-thermal tissue ablation (e.g., any described herein); (b) aremoval apparatus for removing one or more ablated tissue portion(s)(e.g., any described herein); and optionally (c) a positioning apparatusfor positioning skin (e.g., any described herein). In some embodiments,the removal apparatus includes a pin, an adhesive, a probe array, avacuum, a compression element, a laser source, a high-pressure fluidjet, a cryoprobe, a cryosource, a cryoneedle, a multi-hole needleincluding one or more chemical or bioactive agents, a microelectrode, awire, and/or a fiber (e.g., such as any described herein). In otherembodiments, the positioning apparatus includes a tension rod, amicrohook, a microbarb, vacuum, a cryoprobe, a cryosource, an adhesive,a switch, and/or a sensor.

In any of the devices or method herein, the ablative apparatus, theremoval apparatus, and the positioning apparatus are configured in asingle device.

The various embodiments of the present invention may be used to provideablated tissue portions. An ablated tissue portion may have specificdimensions. In some embodiments, an ablated tissue portion has at leastone dimension in a range of about 10 μm to about 2 mm (e.g., about 10 μmto 500 μm, about 10 μm to 100 μm, 10 μm to 250 μm, 10 μm to 500 μm, 10μm to 750 μm, 10 μm to 1 mm, 10 μm to 1.5 mm, 10 μm to 2 mm, about 50 μmto 100 μm, 50 μm to 250 μm, 50 μm to 500 μm, 50 μm to 750 μm, 50 μm to 1mm, 50 μm to 1.5 mm, 50 μm to 2 mm, 100 μm to 250 μm, 100 μm to 500 μm,100 μm to 750 μm, 100 μm to 1 mm, 100 μm to 1.5 mm, 100 μm to 2 mm, 250μm to 500 μm, 250 μm to 750 μm, 250 μm to 1 mm, 250 μm to 1.5 mm, 250 μmto 2 mm, 500 μm to 750 μm, 500 μm to 1 mm, 500 μm to 1.5 mm, 500 μm to 2mm, 750 μm to 1 mm, 750 μm to 1.5 mm, or 750 μm to 2 mm). In someembodiments an ablated tissue portion has an areal dimension less thanabout 2 mm² and/or a volumetric dimension that is less than about 6 mm³.The ablated tissue portion may have an areal dimension in a range ofabout 0.001 mm² to about 2 mm² (e.g., In some embodiments, ablatedtissue portions have an areal dimension less than about 0.2 mm²).

In some embodiments, an ablated tissue portion may form a hole in theskin region, where the diameter or width of the hole is less than about1.0 mm (e.g., less than about 1.0 mm, 750 μm, 500 μm, 250 μm, 100 μm, 50μm, or 10 μm). The ablated tissue portion may form a hole in the skinregion, where the diameter or width is in a range of about 0.01 mm toabout 2 mm (e.g., about 0.01 mm to 0.05 mm, 0.01 to 0.1 mm, 0.01 mm to0.25 mm, 0.01 mm to 0.5 mm, 0.01 mm to 0.75 mm, 0.01 mm to 1 mm, 0.01 mmto 1.5 mm, 0.01 mm to 2 mm, 0.05 to 0.1 mm, 0.05 mm to 0.25 mm, 0.05 mmto 0.5 mm, 0.05 mm to 0.75 mm, 0.05 mm to 1 mm, 0.05 mm to 1.5 mm, 0.05mm to 2 mm, 0.1 mm to 0.25 mm, 0.1 mm to 0.5 mm, 0.1 mm to 0.75 mm, 0.1mm to 1 mm, 0.1 mm to 1.5 mm, 0.1 mm to 2 mm, 0.25 mm to 0.5 mm, 0.25 mmto 0.75 mm, 0.25 mm to 1 mm, 0.25 mm to 1.5 mm, 0.25 mm to 2 mm, 0.5 mmto 0.75 mm, 0.5 mm to 1 mm, 0.5 mm to 1.5 mm, 0.5 mm to 2 mm, 0.75 to 1mm, 0.75 to 1.5 mm, or 0.75 to 2 mm, or any ranges described herein). Insome embodiments, the volumetric dimension is less than or equal toabout 6 mm³ (e.g., as described herein) or between about 0.001 mm³ and 6mm³ (e.g., as described herein). In particular embodiments, ablatedtissue portions are discrete incised tissue or excised tissue portions.The present invention includes ablated tissue portions having width todepth ratios between 1:0.3 to 1:1 (e.g., 1:0.3 to 1:1, 1:0.35 to 1:1,1:0.4 to 1:1, 1:0.45 to 1:1, 1:0.5 to 1:1, 1:1 to 0.55 to 1:1, 1:0.6 to1:1, 1:0.65 to 1:1, 1:0.7 to 1:1, 1:0.75 to 1:1, 1:0.8 to 1:1, 1:0.85 to1:1, 1:0.9 to 1:1, 1:0.95 to 1:1, 1:0.3 to 1:0.95, 1:0.35 to 1:0.95,1:0.4 to 1:0.95, 1:0.45 to 1:0.95, 1:0.5 to 1:0.95, 1:0.95 to 0.55 to1:0.95, 1:0.6 to 1:0.95, 1:0.65 to 1:0.95, 1:0.7 to 1:0.95, 1:0.75 to1:0.95, 1:0.8 to 1:0.95, 1:0.85 to 1:0.95, 1:0.9 to 1:0.95, 1:0.3 to1:0.9, 1:0.35 to 1:0.9, 1:0.4 to 1:0.9, 1:0.45 to 1:0.9, 1:0.5 to 1:0.9,1:0.9 to 0.55 to 1:0.9, 1:0.6 to 1:0.9, 1:0.65 to 1:0.9, 1:0.7 to 1:0.9,1:0.75 to 1:0.9, 1:0.8 to 1:0.9, 1:0.85 to 1:0.9, 1:0.3 to 1:0.85,1:0.35 to 1:0.85, 1:0.4 to 1:0.85, 1:0.45 to 1:0.85, 1:0.5 to 1:0.85,1:0.85 to 0.55 to 1:0.85, 1:0.6 to 1:0.85, 1:0.65 to 1:0.85, 1:0.7 to1:0.85, 1:0.75 to 1:0.85, 1:0.8 to 1:0.85, 1:0.3 to 1:0.8, 1:0.35 to1:0.8, 1:0.4 to 1:0.8, 1:0.45 to 1:0.8, 1:0.5 to 1:0.8, 1:0.8 to 0.55 to1:0.8, 1:0.6 to 1:0.8, 1:0.65 to 1:0.8, 1:0.7 to 1:0.8, 1:0.75 to 1:0.8,1:0.3 to 1:0.75, 1:0.35 to 1:0.75, 1:0.4 to 1:0.75, 1:0.45 to 1:0.75,1:0.5 to 1:0.75, 1:0.75 to 0.55 to 1:0.75, 1:0.6 to 1:0.75, 1:0.65 to1:0.75, 1:0.7 to 1:0.75, 1:0.3 to 1:0.65, 1:0.35 to 1:0.65, 1:0.4 to1:0.65, 1:0.45 to 1:0.65, 1:0.5 to 1:0.65, 1:0.65 to 0.55 to 1:0.65,1:0.6 to 1:0.65, 1:0.3 to 1:0.65, 1:0.35 to 1:0.65, 1:0.4 to 1:0.65,1:0.45 to 1:0.65, 1:0.5 to 1:0.65, 1:0.65 to 0.55 to 1:0.65, 1:0.6 to1:0.65, 1:0.3 to 1:0.6, 1:0.35 to 1:0.6, 1:0.4 to 1:0.6, 1:0.45 to1:0.6, 1:0.5 to 1:0.6, 1:0.6 to 0.55 to 1:0.6, 1:0.3 to 1:0.55, 1:0.35to 1:0.55, 1:0.4 to 1:0.55, 1:0.45 to 1:0.55, 1:0.5 to 1:0.55, 1:0.3 to1:0.5, 1:0.35 to 1:0.5, 1:0.4 to 1:0.5, 1:0.45 to 1:0.5, 1:0.5 to 1:0.5,1:0.3 to 1:0.45, 1:0.35 to 1:0.45, 1:0.4 to 1:0.45, 1:0.3 to 1:0.4,1:0.35 to 1:0.4, or 1:0.3 to 1:0.35) and 1:25 to 1:75 (e.g., 1:25 to1:75, 1:30 to 1:75, 1:35 to 1:75, 1:40 to 1:75, 1:45 to 1:75, 1:50 to1:75, 1:55 to 1:75, 1:60 to 1:75, 1:65 to 1:75, 1:70 to 1:75, 1:25 to1:70, 1:30 to 1:70, 1:35 to 1:70, 1:40 to 1:70, 1:45 to 1:70, 1:50 to1:70, 1:55 to 1:70, 1:60 to 1:70, 1:65 to 1:70, 1:25 to 1:65, 1:30 to1:65, 1:35 to 1:65, 1:40 to 1:65, 1:45 to 1:65, 1:50 to 1:65, 1:55 to1:65, 1:60 to 1:65, 1:25 to 1:60, 1:30 to 1:60, 1:35 to 1:60, 1:40 to1:60, 1:45 to 1:60, 1:50 to 1:60, 1:55 to 1:60, 1:25 to 1:55, 1:30 to1:55, 1:35 to 1:55, 1:40 to 1:55, 1:45 to 1:55, 1:50 to 1:55, 1:25 to1:50, 1:30 to 1:50, 1:35 to 1:50, 1:40 to 1:50, 1:45 to 1:50, 1:25 to1:45, 1:30 to 1:45, 1:35 to 1:45, 1:40 to 1:45, 1:25 to 1:40, 1:30 to1:40, 1:35 to 1:40, 1:25 to 1:35, 1:30 to 1:35, or 1:25 to 1:30).

The invention may also feature ablated tissue portions having a width todepth ratios between about 1:1 to about 1:20 (e.g., 1:1 to 1:2, 1:1 to1:3, 1:1 to 1:4, 1:1 to 1:5, 1:1 to 1:6, 1:1 to 1:7, 1:1 to 1:8, 1:1 to1:9, 1:1 to 1:10, 1:1 to 1:11, 1:1 to 1:12, 1:1 to 1:13, 1:1 to 1:14,1:1 to 1:15, 1:1 to 1:16, 1:1 to 1:17, 1:1 to 1:18, 1:1 to 1:19, 1:1 to1:20, 1:2 to 1:3, 1:2 to 1:4, 1:2 to 1:5, 1:2 to 1:6, 1:2 to 1:7, 1:2 to1:8, 1:2 to 1:9, 1:2 to 1:10, 1:2 to 1:11, 1:2 to 1:2, 1:2 to 1:13, 1:2to 1:14, 1:2 to 1:15, 1:2 to 1:16, 1:2 to 1:17, 1:2 to 1:18, 1:2 to1:19, 1:2 to 1:20, 1:3 to 1:4, 1:3 to 1:5, 1:3 to 1:6, 1:3 to 1:7, 1:3to 1:8, 1:3 to 1:9, 1:3 to 1:10, 1:3 to 1:11, 1:3 to 1:12, 1:3 to 1:13,1:3 to 1:14, 1:3 to 1:15, 1:3 to 1:16, 1:3 to 1:17, 1:3 to 1:18, 1:3 to1:19, 1:3 to 1:20, 1:4 to 1:5, 1:4 to 1:6, 1:4 to 1:7, 1:4 to 1:8, 1:4to 1:9, 1:4 to 1:10, 1:4 to 1:11, 1:4 to 1:12, 1:4 to 1:13, 1:4 to 1:14,1:4 to 1:15, 1:4 to 1:16, 1:4 to 1:17, 1:4 to 1:18, 1:4 to 1:19, 1:4 to1:20, 1:5 to 1:6, 1:5 to 1:7, 1:5 to 1:8, 1:5 to 1:9, 1:5 to 1:10, 1:5to 1:11, 1:5 to 1:12, 1:5 to 1:13, 1:5 to 1:14, 1:5 to 1:15, 1:5 to1:16, 1:5 to 1:17, 1:5 to 1:18, 1:5 to 1:19, 1:5 to 1:20, 1:6 to 1:7,1:6 to 1:8, 1:6 to 1:9, 1:6 to 1:10, 1:6 to 1:11, 1:6 to 1:12, 1:6 to1:13, 1:6 to 1:14, 1:6 to 1:15, 1:6 to 1:16, 1:6 to 1:17, 1:6 to 1:18,1:6 to 1:19, 1:6 to 1:20, 1:7 to 1:8, 1:7 to 1:9, 1:7 to 1:10, 1:7 to1:11, 1:7 to 1:12, 1:7 to 1:13, 1:7 to 1:14, 1:7 to 1:15, 1:7 to 1:16,1:7 to 1:17, 1:7 to 1:18, 1:7 to 1:19, 1:7 to 1:20, 1:8 to 1:9, 1:8 to1:10, 1:8 to 1:11, 1:8 to 1:12, 1:8 to 1:13, 1:8 to 1:14, 1:8 to 1:15,1:8 to 1:16, 1:8 to 1:17, 1:8 to 1:18, 1:8 to 1:19, 1:8 to 1:20, 1:9 to1:10, 1:9 to 1:11, 1:9 to 1:12, 1:9 to 1:13, 1:9 to 1:14, 1:9 to 1:15,1:9 to 1:16, 1:9 to 1:17, 1:9 to 1:18, 1:9 to 1:19, 1:9 to 1:20, 1:10 to1:11, 1:10 to 1:12, 1:10 to 1:13, 1:10 to 1:14, 1:10 to 1:15, 1:10 to1:16, 1:10 to 1:17, 1:10 to 1:18, 1:10 to 1:19, 1:10 to 1:20, 1:11 to1:12, 1:11 to 1:13, 1:11 to 1:14, 1:11 to 1:15, 1:11 to 1:16, 1:11 to1:17, 1:11 to 1:18, 1:11 to 1:19, 1:11 to 1:20, 1:12 to 1:13, 1:12 to1:14, 1:12 to 1:15, 1:12 to 1:16, 1:12 to 1:17, 1:12 to 1:18, 1:12 to1:19, 1:12 to 1:20, 1:13 to 1:14, 1:13 to 1:15, 1:13 to 1:16, 1:13 to1:17, 1:13 to 1:18, 1:13 to 1:19, 1:13 to 1:20, 1:14 to 1:15, 1:14 to1:16, 1:14 to 1:17, 1:14 to 1:18, 1:14 to 1:19, 1:14 to 1:20, 1:15 to1:16, 1:15 to 1:17, 1:15 to 1:18, 1:15 to 1:19, 1:15 to 1:20, 1:17 to1:18, 1:17 to 1:19, or 1:17 to 1:20).

Exemplary ablated tissue portion widths include from about 0.1 mm toabout 0.8 mm (e.g., 0.1 mm to 0.8 mm, 0.1 mm to 0.6 mm, 0.1 mm to 0.4mm, 0.1 mm to 0.2 mm, 0.2 mm to 0.8 mm, 0.2 mm to 0.6 mm, 0.2 mm to 0.4mm, 0.2 mm to 0.3 mm, 0.3 mm to 0.8 mm, 0.3 mm to 0.6 mm, 0.3 mm to 0.4mm, 0.4 mm to 0.8 mm, 0.4 mm to 0.6 mm, 0.4 mm to 0.5 mm, 0.5 mm to 0.8mm, 0.5 mm to 0.6 mm, 0.6 mm to 0.8 mm, 0.6 mm to 0.7 mm, or 0.7 mm to0.8 mm). Exemplary ablated tissue portion widths include from about 0.9mm to about 20 mm (e.g., 0.9 mm to 20 mm, 0.9 mm to 17 mm, 0.9 mm to 14mm, 0.9 mm to 11 mm, 0.9 mm to 8 mm, 0.9 mm to 5 mm, 0.9 mm to 3 mm, 3mm to 20 mm, 3 mm to 17 mm, 3 mm to 14 mm, 3 mm toll mm, 3 mm to 8 mm, 3mm to 5 mm, 5 mm to 20 mm, 5 mm to 17 mm, 5 mm to 14 mm, 5 mm to 11 mm,5 mm to 8 mm, 8 mm to 20 mm, 8 mm to 17 mm, 8 mm to 14 mm, 8 mm to 11mm, 11 mm to 20 mm, 11 mm to 17 mm, 11 mm to 14 mm, 14 mm to 20 mm, 14mm to 17 mm, or 17 mm to 20 mm) and 0.01 mm to 0.25 mm (e.g., 0.01 mm to0.25 mm, 0.02 mm to 0.25 mm, 0.03 mm to 0.25 mm, 0.05 mm to 0.25 mm,0.075 mm to 0.25 mm, 0.1 mm to 0.25 mm, 0.15 mm to 0.25 mm, 0.2 mm to0.25 mm, 0.01 mm to 0.2 mm, 0.02 mm to 0.2 mm, 0.03 mm to 0.2 mm, 0.05mm to 0.2 mm, 0.075 mm to 0.2 mm, 0.1 mm to 0.2 mm, 0.15 mm to 0.2 mm,0.01 mm to 0.15 mm, 0.02 mm to 0.15 mm, 0.03 mm to 0.15 mm, 0.05 mm to0.15 mm, 0.075 mm to 0.15 mm, 0.1 mm to 0.15 mm, 0.01 mm to 0.1 mm, 0.02mm to 0.1 mm, 0.03 mm to 0.1 mm, 0.05 mm to 0.1 mm, 0.075 mm to 0.1 mm,0.01 mm to 0.075 mm, 0.02 mm to 0.075 mm, 0.03 mm to 0.075 mm, 0.05 mmto 0.075 mm, 0.01 mm to 0.05 mm, 0.02 mm to 0.05 mm, 0.03 mm to 0.05 mm,0.01 mm to 0.03 mm, 0.02 mm to 0.03 mm, 0.03 mm to 0.03 mm, 0.01 mm to0.03 mm, 0.02 mm to 0.03 mm, or 0.01 mm to 0.02 mm). Furthernon-limiting exemplary ablated tissue portion widths and/or lengthsinclude from about 0.01 mm to about 20 mm (e.g., 0.01 mm to 1 mm, 0.01mm to 2 mm, 0.01 mm to 5 mm, 0.01 mm to 10 mm, 0.01 mm to 15 mm, 0.05 mmto 1 mm, 0.05 mm to 2 mm, 0.05 mm to 5 mm, 0.05 mm to 10 mm, 0.05 mm to15 mm, 0.05 mm to 20 mm, 0.1 mm to 1 mm, 0.1 mm to 2 mm, 0.1 mm to 5 mm,0.1 mm to 10 mm, 0.1 mm to 15 mm, 0.1 mm to 20 mm, 0.5 mm to 1 mm, 0.5mm to 2 mm, 0.5 mm to 5 mm, 0.5 mm to 10 mm, 0.5 mm to 15 mm, 0.5 mm to20 mm, 1 mm to 2 mm, 1 mm to 5 mm, 1 mm to 10 mm, 1 mm to 15 mm, 1 mm to20 mm, 2 mm to 5 mm, 2 mm to 10 mm, 2 mm to 15 mm, 2 mm to 20 mm, 5 mmto 10 mm, 5 mm to 15 mm, or 5 mm to 20 mm) or from about 0.01 mm toabout 2 mm (e.g., 0.01 mm to 0.1 mm, 0.01 mm to 0.5 mm, 0.01 mm to 1 mm,0.01 mm to 1.5 mm, 0.01 mm to 1.75 mm, 0.05 mm to 0.1 mm, 0.05 mm to 0.5mm, 0.05 mm to 1 mm, 0.05 mm to 1.5 mm, 0.05 mm to 1.75 mm, 0.05 mm to 2mm, 0.1 mm to 0.5 mm, 0.1 mm to 1 mm, 0.1 mm to 1.5 mm, 0.1 mm to 1.75mm, 0.1 mm to 2 mm, 0.3 mm to 0.5 mm, 0.3 mm to 1 mm, 0.3 mm to 1.5 mm,0.3 mm to 1.75 mm, 0.3 mm to 2 mm, 0.5 mm to 1 mm, 0.5 mm to 1.5 mm, 0.5mm to 1.75 mm, 0.5 mm to 2 mm, 0.7 mm to 1 mm, 0.7 mm to 1.5 mm, 0.7 mmto 1.75 mm, 0.7 mm to 2 mm, 1 mm to 1.5 mm, 1 mm to 1.75 mm, 1 mm to 2mm, 1.5 mm to 1.75 mm, 1.5 mm to 2 mm, or 1.75 mm to 2 mm).

In any embodiment described herein, the devices, apparatuses, and/ormethods include the use of one or more therapeutic agents selected fromgrowth factors, analgesics (e.g., an NSAID, a COX-2 inhibitor, anopioid, a glucocorticoid agent, a steroid, or a mineralocorticoid agent,or any described herein), anesthetics (e.g., procaine, amethocaine,cocaine, lidocaine (also known as Lignocaine), prilocaine, bupivacaine,levobupivacaine, ropivacaine, mepivacaine, benzocaine, butamben,dibucaine, oxybuprocaine, pramoxine, proparacaine, proxymetacaine,tetracaine, or dibucaine), antibiotics, antifungals, antiinflammatoryagents, antimicrobials (e.g., chlorhexidine-, iodine-, or silver-basedagents, as described herein), antiseptics (e.g., an alcohol, aquaternary ammonium compound, or any described herein),antiproliferative agents, emollients, hemostatic agents, procoagulativeagents, anticoagulative agents, immune modulators, proteins, vitamins,microparticles (e.g., carbon particles), nanoparticles (e.g., goldnanocomposites), imaging agents (e.g., a radioisotope-containing moietyor a fluorescent-containing moiety), dyes (e.g., an ink, a chromophore,a visible dye, an IR dye, or a fluorescent dye), pigments, tracers, skinwhitening agents (e.g. hydroquinone), vitamin A derivatives (e.g.,tretinoin), or cosmetics (e.g., a cream, a lotion, an emollient, apowder, a perfume, a lipstick, a makeup, a towelette, a hand sanitizer,a butter, and others). In particular embodiments, the therapeutic agentis a hemostatic agent (e.g., a vasoconstrictor, such as epinephrine,pseudoephedrine, cocaine, an amphetamine, an antihistamine, adecongestant, or a stimulant), a procoagulative agent, ananticoagulative agent, or combinations thereof. In some embodiments, thetherapeutic agent is selected from the group of anhydrous aluminumsulfate, anti-fibrinolytic agent(s) (e.g., epsilon aminocaproic acid,tranexamic acid, or the like), anti-platelet agent(s) (e.g., aspirin,dipyridamole, ticlopidine, clopidogrel, or prasugrel), calcium alginate,cellulose, chitosan, coagulation factor(s) (e.g., II, V, VII, VIII, IX,X, XI, XIII, or Von Willebrand factor, as well as activated formsthereof), collagen (e.g., microfibrillar collagen), coumarinderivative(s) or vitamin K antagonist(s) (e.g., warfarin (coumadin),acenocoumarol, atromentin, phenindione, or phenprocoumon), desmopressin,epinephrine, factor Xa inhibitor(s) (e.g., apixaban or rivaroxaban),fibrinogen, heparin or derivatives thereof (e.g., low molecular weightheparin, fondaparinux, or idraparinux), poly-N-acetyl glucosamine,potassium alum, propyl gallate, silver nitrate, thrombin, thrombininhibitor(s) (e.g., argatroban, bivalirudin, dabigatran, hirudin,lepirudin, or ximelagatran), titanium oxide, or a zeolite (e.g., acalcium-loaded zeolite).

In any embodiment described herein, the devices, apparatuses, andmethods are useful for eliminating tissue volume or area, promotingbeneficial tissue growth, tightening skin, rejuvenating skin, improvingskin texture or appearance, removing skin laxity, lifting skin, skinrepositioning, tattoo removal, and/or expanding tissue volume or area.In some embodiments, the devices, apparatuses, and methods are usefulfor treating one or more diseases, disorders, or conditions to improveskin appearance, to rejuvenate skin, and/or to tighten skin. Exemplarydiseases, disorders, or conditions are described herein and includeremoval of pigment, veins (e.g., spider veins or reticular veins),and/or vessels in the skin, as well as treatment of acne, allodynia,blemishes, ectopic dermatitis, hyperpigmentation, hyperplasia (e.g.,lentigo or keratosis), loss of translucency, loss of elasticity, melasma(e.g., epidermal, dermal, or mixed subtypes), photodamage, rashes (e.g.,erythematous, macular, papular, and/or bullous conditions), psoriasis,rhytides (or wrinkles, e.g., crow's feet, age-related rhytides,sun-related rhytides, or heredity-related rhytides), sallow color, scarcontracture (e.g., relaxation of scar tissue), scarring (e.g., due toacne, surgery, or other trauma), skin aging, skin contraction (e.g.,excessive tension in the skin), skin irritation/sensitivity, skin laxity(e.g., loose or sagging skin or other skin irregularities), striae (orstretch marks), vascular lesions (e.g., angioma, erythema, hemangioma,papule, port wine stain, rosacea, reticular vein, or telangiectasia), orany other unwanted skin irregularities (e.g., areas of fibrosis and/ornecrosis).

In other embodiments, the devices, apparatuses, and methods describedherein allow for treatment of uneven surfaces (e.g., the face). Inparticular, large area ablation techniques can be difficult to apply ina conformal or uniform manner to uneven skin surfaces. Thus, the presentinvention allows for conforming to the skin surface, even if the surfaceis uneven.

In other embodiments, the devices, apparatuses, and methods describedherein allow for immediate assessment of the expected or approximateoutcome of the treatment. Compared to energy-based methods, the expectedor approximate outcome of the treatment can be immediately visible. Forinstance, treatment with conventional energy-based devices activatesremodeling of the tissue and the end-result is only visible weeks tomonths after treatment.

In other embodiments, the devices, apparatuses, and methods describedherein allow for rapid healing. For instance, compared to surgery, thetreatment can be much less invasive and the healing can be, therefore,much faster.

The invention also features a method of treating skin including (a)forming a plurality of ablated tissue portions using a 21 G needle; and(b) removing the plurality of ablated tissue portions, wherein 10% ofthe skin within a treatment area is removed. In some embodiments, theplurality of ablated tissue portions are removed with a multiple needlearray. In some embodiments, the treating results in a reduction of skinsurface area. In particular, the reduction in skin surface area occursin a direction orthogonal to Langer lines.

DEFINITIONS

By “ablated tissue portion” is meant that portion of a skin region thatis cut, abraded, damaged, or removed. This term can also mean the skinregion or plug that has been cut or removed. An ablated tissue portionincludes holes in the tissue, for example, having a particular geometry(e.g., a cylindrical geometry), cross-sectional dimension, or width todepth ratio. An ablated tissue portion may also include a microwound, anincised tissue portion, or excised tissue portion. An ablated tissueportion may further be the removed tissue portion resulting from theformation of a hole. An ablated tissue portion may further be thedamaged tissue portion resulting from the formation of a hole by using,e.g., a microwire homogenizer.

By “ablation apparatus” is meant an entity capable of ablating tissue.In particular, the entity may be or include a mechanical mechanism, suchas a needle, drill bit, blade, auger, punch, die, or other entitycapable of ablation of tissue. The entity may be an energy ablationmechanism, such as an electrode, a laser, an RF energy generator, orheating coil. The entity may be a chemical or bioactive agent, mass(e.g., a fluid jet), or a vacuum. The entity may be a component in anarray or a device.

By “about” is meant +/−10% of any recited value.

By “areal dimension” is meant the two-dimensional area of an entity. Thearea of the opening of an ablated tissue portion may be an arealdimension. For example, a circular ablated tissue portion with adiameter of 0.5 mm would have an areal dimension of about 0.2 mm². If acompressive force is applied to skin surrounding the ablated tissueportion, then the opening may be closed, thus reducing the ablatedtissue portion areal dimension to substantially zero, even though theunderlying ablated tissue portion below the surface of the skin stillexists.

By “non-thermal ablation” is meant an ablation technique that does nottransfer thermal energy to the surrounding tissue. Mechanical processescan generate heat but in insufficient amounts to contribute meaningfullyto the desired effect. In one non-limiting embodiment, non-thermalablation includes use of a laser that does not create a coagulationzone.

By “non-thermal ablation apparatus” is meant an entity capable ofnon-thermal ablation.

By “prophylactically treating” a disease, disorder, or condition in asubject is meant reducing the frequency of occurrence or severity of(e.g., preventing) a disease, disorder or condition by affixing a device(e.g., a closure) to the subject prior to the appearance of a symptom ofthe disease, disorder, or condition.

By “serrated cross-sectional dimension” is meant a cross-section of ageometric shape in which the borders visible in the cross-section areirregular and/or undulating.

By “skin-penetrating component” is meant a component that is capable ofpuncturing the skin. Exemplary skin-penetrating components are needles,punches, drill bits, and probes.

By “subject” is meant a human or non-human animal (e.g., a mammal).

By “treating” a disease, disorder, or condition in a subject is meantreducing at least one symptom of the disease, disorder, or condition.

Other features and advantages of the invention will be apparent from thefollowing Detailed Description and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exemplary ablation apparatus having a motor, a depthstop, and a rotating drill bit. Also described in FIG. 1 is theformation of full thickness holes (ablation spanning the completeepidermis and dermis layers) using the ablation apparatus.

FIGS. 2A and 2B show an exemplary ablation drill bit (a spoon bit). FIG.2A is a front view of the drill bit having a u-shaped cutting edge. FIG.2B is a side view of the drill bit having a hemispherical shape withflat surface (front) providing dual cutting edges that may be rotatedaround the drill bit axis.

FIGS. 3A and 3B show exemplary wire or fiber ablation apparatuses. FIG.3A depicts a curved wire attached to the bottom and top ends of aneedle. The needle provides an axis of rotation, allowing the wire to berotated, thus causing the wire to remove a volume of tissue. The shapeof the wire defines the geometry and dimensions of the tissue ablation.FIG. 3B depicts a straight wire attached to axle or needle. The straightwire is attached to the axle at only one end, allowing the wire anadditional degree of freedom during rotation (e.g., moving perpendicularto the longitudinal axis of the axle).

FIG. 4 is a depiction of an exemplary blade array ablation apparatus,each blade apparatus having a square geometry and a cutting edge aroundthe bottom surface. The blade apparatuses are arranged in an array, thusallowing for ablation of multiple tissue portions with a single arraydevice.

FIGS. 5A and 5B provide exemplary high-pressure fluid jet ablationapparatuses having a cylindrical tube structure with a series of holesto eject the fluid in a coherent stream (e.g., a fluid jet). FIG. 5A isa schematic of a high pressure fluid ablation apparatus projecting fluidjets onto the exterior surface of the tissue, thus forming a series ofablated tissue portions. FIG. 5B is a schematic of a high-pressure fluidablation apparatus inserted under the tissue and projecting fluid jetsto the interior of the tissue, thus forming a series of ablated tissueportions.

FIGS. 6A and 6B provide exemplary cryosurgery apparatus having a base tosupport an array of tubes, probes, or needles. FIG. 6A depicts an arrayof cryoprobes, each of which may ablate tissue at the interface betweenthe probe and the tissue. FIG. 6B depicts an array of cryoneedles, eachof which may ablate tissue with cold temperature upon contact.

FIG. 7 shows an exemplary chemical ablation apparatus array having aseries of needles capable of delivering a chemical or bioactive agent.FIG. 7 depicts the chemical or bioactive ablation apparatus having amulti-hole needle, in which holes along the cylindrical body of theneedle allow for transfer of a chemical or bioactive agent at acontrolled depth or location.

FIG. 8 shows an exemplary electroporation apparatus for ablation oftissue having an array of miniature needle-electrodes, each of which hasan active electrode and a return electrode to form a bipolar electrodepair, and a generator to supply electrical energy to the electrodes.

FIG. 9 shows an exemplary electrode or needle-electrode having acylindrical body made of an electrically insulating material, a singlebi-polar electrode where the active and return electrodes are separatedby the insulating material.

FIGS. 10A and 10B show an exemplary tissue removal array apparatushaving a support layer and an adhesive layer. FIG. 10A depicts a flatadhesive layer covering the support layer and removal of tissue byadhesion of the tissue to the adhesive layer. FIG. 10B depicts adhesivelayers affixed to the ends of probes attached to the support layer. FIG.10B also depicts the removal of tissue by adhesion of the tissue to theadhesive layer on the end of the probe.

FIG. 11 shows an exemplary tissue removal array apparatus having ahousing which can sustain a vacuum and an array of holes. FIG. 11depicts the removal of tissue by adherence of tissue by a partial orcomplete vacuum seal to a hole of the array.

FIG. 12 shows an exemplary tissue removal apparatus having a thermalablation source (e.g., a laser) and a micro-coring or blade ablationapparatus. FIG. 12 depicts an exemplary method of tissue removal inwhich the blade ablation device isolates the tissue to be ablated fromthe surrounding tissue. Once the tissue is isolated, a thermal ablationdevice can ablate the tissue inside the blade ablation device, thusremoving the tissue. The blade ablation device insulates the surroundingtissue from the thermal ablation, thus preventing coagulation of thesurrounding tissue.

FIG. 13 shows an exemplary tissue positioning apparatus including twocylindrical rods to provide tension to a tissue area prior to, during,or after ablation or tissue removal. The application of tension to theskin region may provide a flat, more even surface for skin treatment.

FIG. 14 shows an exemplary tissue positioning apparatus having a seriesof micro-hooks that can be attached to and hold tension in a tissue orskin region. The micro-hooks may be distributed to provide tension tothe skin in order to provide a tensioned or flat surface in a variety ofgeometric configurations (shown as square region in FIG. 14).

FIG. 15 shows an exemplary tissue positioning apparatus having a tubefor applying vacuum around a tissue area to be ablated. The vacuumprovides a seal between the tube and the tissue region, thus providingtension across the area. An ablation apparatus (shown as an array ofneedles) may be included inside the vacuum tube to ablate the skinregion while the vacuum positions the tissue.

FIG. 16 shows an exemplary tissue positioning apparatus having a housingconfigured to control the temperature at the tissue interfacing surfaceand providing access through the housing for an ablation apparatus orarray of ablation apparatuses. The temperature at the interface betweenthe positioning device and the tissue surface is lowered until thetissue is held in place by the device.

FIG. 17 shows an exemplary tissue positioning apparatus having a housingincluding an adhesive layer on one surface and providing access throughthe housing for an ablation apparatus or array of ablation apparatuses.A tissue layer under tension may adhere to the adhesive layer, thuspositioning and providing tension to the tissue layer.

FIG. 18 shows the healing progression after treatment with micro-coringneedles on the skin of a Yorkshire pig.

FIG. 19 shows photographs of areas of the abdomen of human subjectstreated with different needle sizes immediately after treatment.

FIG. 20 shows several graphs indicating the change in lineardimension/surface area of a treated square area (21G/10% or 22G/10%) incomparison with a contra-lateral non-treated area of similar dimension(control).

FIG. 21 shows a sequence of photographs taken before and after treatmentof abdominal skin of a human subject.

FIG. 22 shows an exemplary tissue positioning apparatus including twocylindrical pinching rods to provide tension (e.g., a compressive forceapplied across the skin, indicated by arrows) to a tissue area. Theapplication of tension to the skin region may provide a protrudedsurface region of the skin in which the dermis is lifted from underlyinglayers (e.g., subcutaneous fat and muscle), for skin treatment usingmicro-corning needles placed between the pinching rods.

FIG. 23 shows an exemplary tissue positioning apparatus having a seriesof needles (“needle grippers”) that surround micro-corning needles toattach and hold tension (e.g., a gripping force) in a tissue or skinregion. The needle grippers may be inserted in the skin (arrow 1) andpulled (arrow 2) to provide tension to the skin and lift the dermis fromunderlying skin layers. Top figure provides a side-view and bottomfigure provides a top-view of the apparatus.

DETAILED DESCRIPTION

This invention relates to methods and devices for treating skin (e.g.,eliminating tissue volume, tightening skin, lifting skin, and/orreducing skin laxity) by selectively opening or closing a plurality ofwounds or holes (e.g., ablated tissue portions) formed by ablation(e.g., incision or excision of tissue) without thermal energy beingimparted to the surrounding (e.g., non-ablated) tissue. For example,non-thermal ablation can be performed by fractional ablation of theepidermal and/or dermal layer of the skin using a mechanical method,such as a hollow coring needle, a drill, a microauger, a tube comprisingcutting teeth, a spoon bit, a wire, or a fiber, by a fractional ablationusing a high-pressure fluid jet, by fractional cryosurgery using acryoprobe or cryoneedle, by a fractional chemical ablation, byfractional electroporation, by a femtosecond laser, and/or by fractionalvacuum ablation. The methods and apparatuses of the invention alsoinclude skin removal methods. Thermal ablation methods may be used, suchas fractional laser ablation or fractional radio-frequency (RF)ablation, to remove portions of a skin region to be ablated once theregion is thermally isolated from the surrounding tissue, thereby nottransferring thermal energy to the surrounding tissue. The presentinvention also features tissue positioning methods and apparatuses. Thepresent invention may include methods and devices for non-thermalablation, tissue removal, tissue positioning, and combinations thereof.

In particular embodiments, the present invention provides one or more ofthe following advantages. First, the methods and devices herein enablevisualization of results in real time during the course of thetreatment. One can envision asking the patient for feedback in real timeduring the treatment and adjusting the tightening to the patientpreference. Second, the apparatuses include micro-sized features, whichcan be beneficial for controlling the extent of skin treatment. Third,the methods and apparatuses described herein may require less skill thanthat of a surgeon. One can envision treatment of patients in anoutpatient setting, rather than requiring an inpatient, surgicalsetting. Fourth, the methods and apparatuses herein constitute minimallyinvasive techniques, which can provide more predictable results and/orrisk factors than that for more invasive techniques (e.g., plasticsurgery) or non-invasive energy-based techniques (e.g., laser,radiofrequency (RF), or ultrasound). Fifth, the non-thermal fractionalablation methods and apparatuses herein allow skin tightening, skinlifting, and reduction of skin laxity without inducing coagulation inthe surrounding tissue. Thermal ablation techniques prevent and/orinhibit skin tightening by allowing coagulation of the tissue andformation of rigid tissue cores that cannot be compressed. Sixth, themethods and apparatuses herein can allow for rapid closing of holes orslits after treating the skin (e.g., within a few seconds after treatingskin, such as within ten seconds), thereby minimizing the extent ofbleeding and/or clotting within the holes or slits and/or scarformation. Seventh, the methods and apparatuses herein can be useful formaximizing the tightening effect while minimizing healing time byoptimizing tightening (e.g., by controlling the extent of skin pleating,such as by increasing the extent of skin pleating for some applicationsor skin regions and by decreasing the extent of skin pleating for otherapplications or skin regions, as described herein). Eighth, the methodsand apparatuses for tissue removal described herein provide efficientclearance of partially ablated tissue and debris from ablated tissueportions, thus reducing the time for healing and improving the skintightening treatment. Finally, the methods and apparatuses for skinpositioning described herein allow for efficient and effectivepositioning of skin prior to, during, and after ablation and/or tissueremoval. Positioning the skin is critical to control skin-tighteningdirection and ensure ablation occurs in the desired location and desireddimensions.

In some embodiments, apparatuses and methods of the invention allow forthe treatment of skin with varied thickness. Skin regions vary inthickness depending on the location on the body. For example,Kakasheva-Mazenkovska et al., (Contributions, Soc. Biol. Med. Sci.,MASA, XXXII, 2, p. 119-128 (2011), incorporated by reference herein inits entirety) describes thin skin regions for 23-53 year old adults asincluding the anterior lower leg (average skin thickness of 1.7 mm) andthe cheeks (average skin thickness of 2.1 mm) and thick skin regions asthe anterior leg (average skin thickness of 4.9 mm, e.g., in theanterior upper leg) and the gluteus (average skin thickness of 5.2 mm).The thinnest skin region observed across all age groups studied wasabout 0.9 mm, while the thickest skin region observed across all agegroups was about 5.9 mm. To allow for effective skin tightening,ablative tissue portions with a diameter of between 100 μm and 800 μm(e.g., 100, 200, 300, 400, 500, 600, 700, 800 μm) may be desirable. Insome embodiments, ablative tissue portions with a diameter of between200 μm and 700 μm may be desirable. In some embodiments, ablative tissueportions with a diameter of between 300 μm and 500 μm may be desirable.In other embodiments, ablative tissue portions with a diameter ofbetween 500 μm and 800 μm may be desirable. Maintaining the desireddiameter may require the ablation apparatus to provide width to depthratios across a large range (e.g., from 1:0.3 to 1:75).

Ablated Tissue Portions

The present invention features methods, apparatuses and devices forgenerating ablated tissue portions having various geometric dimensions.For instance, the tissue portions can have a width to depth ratio ofbetween about 1:0.3 to about 1:75. In another non-limiting example, thetissue portions have a change in width as a function of depth (e.g., achange in width of between about 10 μm to about 1000 μm as a function ofdepth, e.g., 10 μm to 50 μm, 10 μm to 100 μm, 10 μm to 250 μm, 10 μm to500 μm, 10 μm to 750 μm, 25 μm to 50 μm, 25 μm to 100 μm, 25 μm to 250μm, 25 μm to 500 μm, 25 μm to 750 μm, 25 μm to 1000 μm, 50 μm to 100 μm,50 μm to 250 μm, 50 μm to 500 μm, 50 μm to 750 μm, 50 μm to 1000 μm, 75μm to 100 μm, 75 μm to 150 μm, 75 μm to 200 μm, 75 μm to 250 μm, 75 μmto 300 μm, 75 μm to 350 μm, 75 μm to 400 μm, 75 μm to 450 μm, 75 μm to500 μm, 75 μm to 600 μm, 75 μm to 750 μm, 75 μm to 900 μm, 75 μm to 1000μm, 100 μm to 200 μm, 100 μm to 250 μm, 100 μm to 300 μm, 100 μm to 350μm, 100 μm to 400 μm, 100 μm to 450 μm, 100 μm to 500 μm, 100 μm to 750μm, 100 μm to 900 μm, 100 μm to 1000 μm, 150 μm to 250 μm, 150 μm to 500μm, 150 μm to 750 μm, 150 μm to 1000 μm, 200 μm to 250 μm, 200 μm to 500μm, 200 μm to 750 μm, 200 μm to 1000 μm, 250 μm to 500 μm, 250 μm to 750μm, 250 μm to 1000 μm, 400 μm to 500 μm, 400 μm to 750 μm, 400 μm to1000 μm, 500 μm to 750 μm, 500 μm to 1000 μm, or 750 μm to 1000 μm).

In yet other embodiments, the tissue portions can include a serratedcross-sectional dimension. In some embodiments the ablated tissueportions of the invention have at least one dimension between about 10μm and about 2 mm. In other embodiments, an ablated tissue portion hasan areal dimension of less than about 2.0 mm². In additionalembodiments, an ablated tissue portion has a volume of less than about6.0 mm³. These embodiments are further described below.

An ablated tissue portion may have specific dimensions. In someembodiments, an ablated tissue portion has at least one dimension in arange of about 10 μm to about 2 mm (e.g., about 10 μm to 500 μm, about10 μm to 100 μm, 10 μm to 250 μm, 10 μm to 500 μm, 10 μm to 750 μm, 10μm to 1 mm, 10 μm to 1.5 mm, 10 μm to 2 mm, about 50 μm to 100 μm, 50 μmto 250 μm, 50 μm to 500 μm, 50 μm to 750 μm, 50 μm to 1 mm, 50 μm to 1.5mm, 50 μm to 2 mm, 100 μm to 250 μm, 100 μm to 500 μm, 100 μm to 750 μm,100 μm to 1 mm, 100 μm to 1.5 mm, 100 μm to 2 mm, 250 μm to 500 μm, 250μm to 750 μm, 250 μm to 1 mm, 250 μm to 1.5 mm, 250 μm to 2 mm, 500 μmto 750 μm, 500 μm to 1 mm, 500 μm to 1.5 mm, 500 μm to 2 mm, 750 μm to 1mm, 750 μm to 1.5 mm, or 750 μm to 2 mm). In some embodiments an ablatedtissue portion has an areal dimension less than about 2 mm² and/or avolumetric dimension that is less than about 6 mm³. The ablated tissueportion may have an areal dimension in a range of about 0.001 mm² toabout 2 mm². In some embodiments, ablated tissue portions have an arealdimension less than about 0.2 mm².

In some embodiments, an ablated tissue portion may form a hole in theskin region, where the diameter or width of the hole is less than about1.0 mm (e.g., less than about 1.0 mm, 750 μm, 500 μm, 250 μm, 100 μm, 50μm, or 10 μm). The ablated tissue portion may form a hole in the skinregion, where the diameter or width is in a range of about 0.01 mm toabout 2 mm (e.g., about 0.01 mm to 0.05 mm, 0.01 to 0.1 mm, 0.01 mm to0.25 mm, 0.01 mm to 0.5 mm, 0.01 mm to 0.75 mm, 0.01 mm to 1 mm, 0.01 mmto 1.5 mm, 0.01 mm to 2 mm, 0.05 to 0.1 mm, 0.05 mm to 0.25 mm, 0.05 mmto 0.5 mm, 0.05 mm to 0.75 mm, 0.05 mm to 1 mm, 0.05 mm to 1.5 mm, 0.05mm to 2 mm, 0.1 mm to 0.25 mm, 0.1 mm to 0.5 mm, 0.1 mm to 0.75 mm, 0.1mm to 1 mm, 0.1 mm to 1.5 mm, 0.1 mm to 2 mm, 0.25 mm to 0.5 mm, 0.25 mmto 0.75 mm, 0.25 mm to 1 mm, 0.25 mm to 1.5 mm, 0.25 mm to 2 mm, 0.5 mmto 0.75 mm, 0.5 mm to 1 mm, 0.5 mm to 1.5 mm, 0.5 mm to 2 mm, 0.75 to 1mm, 0.75 to 1.5 mm, or 0.75 to 2 mm, or any ranges described herein). Insome embodiments, the volumetric dimension that is less than or equal toabout 6 mm³ (e.g., as described herein) or between about 0.001 mm³ and 6mm³ (e.g., as described herein). In particular embodiments, ablatedtissue portions are discrete incised tissue or excised tissue portions.

The ablated tissue portion can have any combination of the dimensionsdescribed herein. For instance, in some non-limiting embodiments, theablated tissue portion has at least one dimension that is less thanabout 2 mm and an areal dimension that is less than about 2 mm². Inother embodiments, the ablated tissue portion has at least one dimensionthat is less than about 2 mm and a volumetric dimension that is lessthan about 6 mm³. In yet other embodiments, the ablated tissue portionhas at least one dimension that is less than about 2 mm and an arealdimension that is less than about 2 mm² and a volumetric dimension thatis less than about 6 mm³. In some embodiments, the ablated tissueportion has an areal dimension that is less than about 2 mm² and avolumetric dimension that is less than about 6 mm³.

Width-to-Depth Ratio

The present invention allows for tissue portions having particularwidth-to-depth ratios. Benefits for optimizing such ratios includeimproved skin tightening, treatment of thin skin regions (e.g., loweranterior leg and cheeks), treatment of thick skin (e.g., anterior legand gluteus), and improving skin rejuvenation (e.g., skin texture,color, and/or architecture). More importantly, an optimized width todepth ratio minimizes the risk of scarring while maximizing skintightening. Non-thermal ablation forming ablated tissue portions withspecific width to depth ratios improves healing time, treatment toabnormal skin areas, and increase the ability to tune hole depth anddiameter to the treatment objective. Exemplary width to depth ratiosinclude ratios between 1:0.3 to 1:1 (e.g., 1:0.3 to 1:1, 1:0.35 to 1:1,1:0.4 to 1:1, 1:0.45 to 1:1, 1:0.5 to 1:1, 1:1 to 0.55 to 1:1, 1:0.6 to1:1, 1:0.65 to 1:1, 1:0.7 to 1:1, 1:0.75 to 1:1, 1:0.8 to 1:1, 1:0.85 to1:1, 1:0.9 to 1:1, 1:0.95 to 1:1, 1:0.3 to 1:0.95, 1:0.35 to 1:0.95,1:0.4 to 1:0.95, 1:0.45 to 1:0.95, 1:0.5 to 1:0.95, 1:0.95 to 0.55 to1:0.95, 1:0.6 to 1:0.95, 1:0.65 to 1:0.95, 1:0.7 to 1:0.95, 1:0.75 to1:0.95, 1:0.8 to 1:0.95, 1:0.85 to 1:0.95, 1:0.9 to 1:0.95, 1:0.3 to1:0.9, 1:0.35 to 1:0.9, 1:0.4 to 1:0.9, 1:0.45 to 1:0.9, 1:0.5 to 1:0.9,1:0.9 to 0.55 to 1:0.9, 1:0.6 to 1:0.9, 1:0.65 to 1:0.9, 1:0.7 to 1:0.9,1:0.75 to 1:0.9, 1:0.8 to 1:0.9, 1:0.85 to 1:0.9, 1:0.3 to 1:0.85,1:0.35 to 1:0.85, 1:0.4 to 1:0.85, 1:0.45 to 1:0.85, 1:0.5 to 1:0.85,1:0.85 to 0.55 to 1:0.85, 1:0.6 to 1:0.85, 1:0.65 to 1:0.85, 1:0.7 to1:0.85, 1:0.75 to 1:0.85, 1:0.8 to 1:0.85, 1:0.3 to 1:0.8, 1:0.35 to1:0.8, 1:0.4 to 1:0.8, 1:0.45 to 1:0.8, 1:0.5 to 1:0.8, 1:0.8 to 0.55 to1:0.8, 1:0.6 to 1:0.8, 1:0.65 to 1:0.8, 1:0.7 to 1:0.8, 1:0.75 to 1:0.8,1:0.3 to 1:0.75, 1:0.35 to 1:0.75, 1:0.4 to 1:0.75, 1:0.45 to 1:0.75,1:0.5 to 1:0.75, 1:0.75 to 0.55 to 1:0.75, 1:0.6 to 1:0.75, 1:0.65 to1:0.75, 1:0.7 to 1:0.75, 1:0.3 to 1:0.65, 1:0.35 to 1:0.65, 1:0.4 to1:0.65, 1:0.45 to 1:0.65, 1:0.5 to 1:0.65, 1:0.65 to 0.55 to 1:0.65,1:0.6 to 1:0.65, 1:0.3 to 1:0.65, 1:0.35 to 1:0.65, 1:0.4 to 1:0.65,1:0.45 to 1:0.65, 1:0.5 to 1:0.65, 1:0.65 to 0.55 to 1:0.65, 1:0.6 to1:0.65, 1:0.3 to 1:0.6, 1:0.35 to 1:0.6, 1:0.4 to 1:0.6, 1:0.45 to1:0.6, 1:0.5 to 1:0.6, 1:0.6 to 0.55 to 1:0.6, 1:0.3 to 1:0.55, 1:0.35to 1:0.55, 1:0.4 to 1:0.55, 1:0.45 to 1:0.55, 1:0.5 to 1:0.55, 1:0.3 to1:0.5, 1:0.35 to 1:0.5, 1:0.4 to 1:0.5, 1:0.45 to 1:0.5, 1:0.5 to 1:0.5,1:0.3 to 1:0.45, 1:0.35 to 1:0.45, 1:0.4 to 1:0.45, 1:0.3 to 1:0.4,1:0.35 to 1:0.4, or 1:0.3 to 1:0.35) and 1:25 to 1:75 (e.g., 1:25 to1:75, 1:30 to 1:75, 1:35 to 1:75, 1:40 to 1:75, 1:45 to 1:75, 1:50 to1:75, 1:55 to 1:75, 1:60 to 1:75, 1:65 to 1:75, 1:70 to 1:75, 1:25 to1:70, 1:30 to 1:70, 1:35 to 1:70, 1:40 to 1:70, 1:45 to 1:70, 1:50 to1:70, 1:55 to 1:70, 1:60 to 1:70, 1:65 to 1:70, 1:25 to 1:65, 1:30 to1:65, 1:35 to 1:65, 1:40 to 1:65, 1:45 to 1:65, 1:50 to 1:65, 1:55 to1:65, 1:60 to 1:65, 1:25 to 1:60, 1:30 to 1:60, 1:35 to 1:60, 1:40 to1:60, 1:45 to 1:60, 1:50 to 1:60, 1:55 to 1:60, 1:25 to 1:55, 1:30 to1:55, 1:35 to 1:55, 1:40 to 1:55, 1:45 to 1:55, 1:50 to 1:55, 1:25 to1:50, 1:30 to 1:50, 1:35 to 1:50, 1:40 to 1:50, 1:45 to 1:50, 1:25 to1:45, 1:30 to 1:45, 1:35 to 1:45, 1:40 to 1:45, 1:25 to 1:40, 1:30 to1:40, 1:35 to 1:40, 1:25 to 1:35, 1:30 to 1:35, or 1:25 to 1:30).Additional width-to-depth ratios are described herein, such as 1:1 toabout 1:20 (e.g., any range described herein).

Exemplary ablated tissue portion widths include from about 0.1 mm toabout 0.8 mm (e.g., 0.1 mm to 0.8 mm, 0.1 mm to 0.6 mm, 0.1 mm to 0.4mm, 0.1 mm to 0.2 mm, 0.2 mm to 0.8 mm, 0.2 mm to 0.6 mm, 0.2 mm to 0.4mm, 0.2 mm to 0.3 mm, 0.3 mm to 0.8 mm, 0.3 mm to 0.6 mm, 0.3 mm to 0.4mm, 0.4 mm to 0.8 mm, 0.4 mm to 0.6 mm, 0.4 mm to 0.5 mm, 0.5 mm to 0.8mm, 0.5 mm to 0.6 mm, 0.6 mm to 0.8 mm, 0.6 mm to 0.7 mm, or 0.7 mm to0.8 mm). Exemplary ablated tissue portion widths includes 0.9 mm to 20mm (e.g., 0.9 mm to 20 mm, 0.9 mm to 17 mm, 0.9 mm to 14 mm, 0.9 mm to11 mm, 0.9 mm to 8 mm, 0.9 mm to 5 mm, 0.9 mm to 3 mm, 3 mm to 20 mm, 3mm to 17 mm, 3 mm to 14 mm, 3 mm to 11 mm, 3 mm to 8 mm, 3 mm to 5 mm, 5mm to 20 mm, 5 mm to 17 mm, 5 mm to 14 mm, 5 mm to 11 mm, 5 mm to 8 mm,8 mm to 20 mm, 8 mm to 17 mm, 8 mm to 14 mm, 8 mm to 11 mm, 11 mm to 20mm, 11 mm to 17 mm, 11 mm to 14 mm, 14 mm to 20 mm, 14 mm to 17 mm, or17 mm to 20 mm) and 0.01 mm to 0.25 mm (e.g., 0.01 mm to 0.25 mm, 0.02mm to 0.25 mm, 0.03 mm to 0.25 mm, 0.05 mm to 0.25 mm, 0.075 mm to 0.25mm, 0.1 mm to 0.25 mm, 0.15 mm to 0.25 mm, 0.2 mm to 0.25 mm, 0.01 mm to0.2 mm, 0.02 mm to 0.2 mm, 0.03 mm to 0.2 mm, 0.05 mm to 0.2 mm, 0.075mm to 0.2 mm, 0.1 mm to 0.2 mm, 0.15 mm to 0.2 mm, 0.01 mm to 0.15 mm,0.02 mm to 0.15 mm, 0.03 mm to 0.15 mm, 0.05 mm to 0.15 mm, 0.075 mm to0.15 mm, 0.1 mm to 0.15 mm, 0.01 mm to 0.1 mm, 0.02 mm to 0.1 mm, 0.03mm to 0.1 mm, 0.05 mm to 0.1 mm, 0.075 mm to 0.1 mm, 0.01 mm to 0.075mm, 0.02 mm to 0.075 mm, 0.03 mm to 0.075 mm, 0.05 mm to 0.075 mm, 0.01mm to 0.05 mm, 0.02 mm to 0.05 mm, 0.03 mm to 0.05 mm, 0.01 mm to 0.03mm, 0.02 mm to 0.03 mm, 0.03 mm to 0.03 mm, 0.01 mm to 0.03 mm, 0.02 mmto 0.03 mm, or 0.01 mm to 0.02 mm). Further non-limiting exemplaryablated tissue portion widths and/or lengths include from about 0.01 mmto about 20 mm or from about 0.01 mm to about 2 mm (e.g., such as anyrange described herein).

Changes in Width Along the Depth

The present invention allows for tissue portions having changes inwidth. Benefits for optimizing such changes include improved ablatedtissue portion closing (e.g., a larger diameter at skin surface andsmaller diameter in the skin depth will facilitate hole closing or,alternatively, a small diameter at skin surface and larger diameter inskin depth may accelerate closure of the epidermal layer and thereforeminimize risk of adverse events, such as infections, and minimizehealing time), increased surface area of the inside of the ablatedtissue portion or hole, or improved directional healing response byhaving an offset increase of diameter, thus biasing hole closure uponcompression in a single direction. Exemplary changes include a change inwidth of between about 10 μm to about 1000 μm as a function of depth,such as any range described herein. In one non-limiting embodiment, thechange is about 100 μm at the skin surface and about 500 μm at thebottom of the dermal layer (e.g., to minimize closure time of theepidermal layer, such as reepithelialization). In another non-limitingembodiment, the change is about 400 μm at the skin surface and betweenabout 0 to about 200 μm at the bottom of the dermal layer (e.g., tofacilitate hole mechanical closure).

Serrated Cross-Sectional Dimension

The present invention also allows for tissue portions having a serratedor scalloped cross-sectional dimension. Benefits for serratedcross-sectional dimensions include increased surface area for bindingtissue together with or without glues or sealants, thus improving thestrength of a closure. In addition, serrated edges provide a mechanismto bias hole closing. For example, the serrated internal pattern of anablated tissue portion may be configured such that when compressed in afirst direction, the serrated structures from opposite sides of thewound interlock, thus allowing complete closure of the hole. In someembodiments, the serrated or scalloped cross-sectional dimensions occurin the x-axis, y-axis, or xy-axis. In other embodiments, the serrated orscalloped cross-sectional dimensions occur in the z-axis. Exemplaryserrated cross-sectional dimensions include regular or irregular ridgesor depressions in the side wall of an ablated tissue portion or holeequal in height to 10% of the hole diameter. In other embodiments, theheight of the regular or irregular ridges or depressions is between 5%and 70% of the diameter of the ablated tissue portion (e.g., between 5%and 10%, 5% and 20%, 5% and 30%, 5% and 40%, 5% and 50%, 5% and 60%, 5%and 70%, 10% and 20%, 10% and 30%, 10% and 40%, 10% and 50%, 10% and60%, 10% and 70%, 20% and 30%, 20% and 40%, 20% and 50%, 20% and 60%,20% and 70%, 30% and 40%, 30% and 50%, 30% and 60%, 30% and 70%, 40% and50%, 40% and 60%, 40% and 70%, 50% and 60%, 50% and 70%, or 60% and70%).

Ablation Apparatuses and Methods for Non-Thermal Ablation of Tissue

The present invention features methods, apparatuses and devices forgenerating ablated tissue portions (e.g., microwounds or incised orexcised tissue portions) without imparting thermal energy to thesurrounding tissue. Exemplary devices include those which selectivelygenerate an ablated tissue portion using a drill, driver (e.g., a piledriver (e.g., a tattoo gun that uses solid needles), which compresses,shears, and destroys the tissue as it cycles up and down in the z-axis),wire or flexible fiber, blade, high pressure fluid jet, cryoprobes orcryoneedles, chemical treatment, non-thermal energy, or direct vacuum.In particular, wounds generated without the use of thermal energy bymethods and devices of this invention may desirably have an arealdimension of less than 4 mm² and/or a volumetric dimension that is lessthan about 6 mm³. Methods and devices for non-thermal ablation may formholes with multiple diameters along the wound depth. The presentinvention also features methods and devices for making ablated tissueportions with serrated or non-uniform edges along the depth of theablated tissue portion. One or more therapeutic agents (e.g. ananticoagulant) may be added prior to, during, or after ablation oftissue.

Drills

The present invention features methods, devices, and apparatuses forrotating a penetrating component that may be used to ablate skin in afractional pattern. The mechanical fractional ablation apparatusincludes a motor (e.g., electric or pneumatic motor) for rotation of apenetrating component or an array of penetrating components.

The penetrating component is positioned to be in contact with the skinouter surface (epidermis), the motor is activated, and the apparatus ispushed toward the skin until it reaches a pre-set depth. An optionaladjustable depth stop may limit the ablation depth. The ablation depthmay be adjusted to remove only a portion of the skin (i.e., epidermisand part of the dermis) or to remove the full epidermis and dermisthickness. Full thickness removal may be beneficial for skin tightening.Removing only part of the thickness of the skin region may be beneficialfor improvement of the tissue texture and/or color and/or to acceleratehealing. In one embodiment, a penetrating component may be a drill bithaving spiral channels along its long axis to carve away the tissue andcreate the ablation and carry the tissue up the bit as it turns.

Ablative apparatuses may be designed to spin at a range of rotationalspeeds (e.g., greater than 50 rpm or between about 50 rpm to about 2500rpm) that may be selected to produce the desired effect (e.g., ablationcreates well defined regions of tissue with clean margins), whilereducing or eliminating undesirable effects, such as heat production andtissue shredding. In another embodiment, a drill includes micro-augersin which the penetrating component consists of a spiral flange forcutting into the tissue and conveying the tissue up to the surface ofthe skin for elimination. In particular non-limiting embodiments, itmight be beneficial to work at lower speed to minimize heating of thetissue and to improve cutting performance through soft materials. Inthis context, an exemplary non-limiting maximal rotational speed isabout 2500 rpm while allowing for very low speeds above about 50 rpm.Exemplary rotational speeds include from about 50 rpm to about 2500 rpm(e.g., 50 rpm to 100 rpm, 50 rpm to 250 rpm, 50 rpm to 500 rpm, 50 rpmto 750 rpm, 50 rpm to 1000 rpm, 50 rpm to 1500 rpm, 50 rpm to 2000 rpm,50 rpm to 2500 rpm, 75 rpm to 100 rpm, 75 rpm to 250 rpm, 75 rpm to 500rpm, 75 rpm to 750 rpm, 75 rpm to 1000 rpm, 75 rpm to 1500 rpm, 75 rpmto 2000 rpm, 75 rpm to 2500 rpm, 100 rpm to 250 rpm, 100 rpm to 500 rpm,100 rpm to 750 rpm, 100 rpm to 1000 rpm, 100 rpm to 1500 rpm, 100 rpm to2000 rpm, 100 rpm to 2500 rpm, 250 rpm to 500 rpm, 250 rpm to 750 rpm,250 rpm to 1000 rpm, 250 rpm to 1500 rpm, 250 rpm to 2000 rpm, 250 rpmto 2500 rpm, 500 rpm to 750 rpm, 500 rpm to 1000 rpm, 500 rpm to 1500rpm, 500 rpm to 2000 rpm, 500 rpm to 2500 rpm, 750 rpm to 1000 rpm, 750rpm to 1500 rpm, 750 rpm to 2000 rpm, 750 rpm to 2500 rpm, 1000 rpm to1500 rpm, 1000 rpm to 2000 rpm, 1000 rpm to 2500 rpm, 1500 rpm to 2000rpm, 1500 rpm to 2500 rpm, or 2000 rpm to 2500 rpm).

Alternatively, a micro-auger may be configured to move tissue and debristo another region where it may be eliminated. For example, the flangemay have a spiral configured to push the cuttings downward away from thesite of ablation. A spiral channel or flange may be on a portion of thepenetrating component or along its entire length. The cuttings may beremoved in a second step or left to be resorbed by the body in asubdermal location.

Many drill bit designs are contemplated, including drill bits which areemployed for use in non-medical fields such as construction,engineering, and general mechanical applications. The drill bits may befashioned from a wide variety of materials; non-limiting examplesinclude: metals, plastics, silicon, crystalline materials, and noncrystalline materials. The drill bits may be hollow or solid. Hollowdrills may be fashioned to have a channel through their core thatconveys a vacuum for elimination of tissue cuttings. Penetratingcomponents may be cooled or heated to control the temperature of thesurrounding tissue. The pattern of the flange or spiral channels may befashioned to optimize the ablation and/or transport of tissue such asadipose tissue, dermis, or epidermal tissue.

In another embodiment, drilling through soft tissue (e.g., skin) may beachieved with a hollow tube having a sharp cutting edge (e.g., a paperdrill). Ablated tissue is captured in the hollow drill bit.Alternatively, the hollow tube may be pushed through the skin by ahigh-frequency vibrating mechanism (e.g., a piezo actuator operated athigh frequency). In another alternative, a tube having a sharp edge andcutting teeth (e.g., a hole saw) may be used. Similarly, tissue iscaptured in the hollow drill bit. A spoon bit may also be used to ablatetissue. A spoon bit is constituted of a grooved shank and is shaped likethe bowl of a spoon. The edges of the bit are sharp and cut throughtissue.

In another embodiment, tissue may be hardened before drilling, e.g., bylocal freezing. This allows use of twist drill bits having a cuttingpoint at the tip of a cylindrical shaft with helical flutes for removalof cut tissue. Freezing may be achieved by application of a freezingagent (e.g. liquid nitrogen or argon gas) or by application of afreezing probe on the skin surface. Alternatively, a drill bit may becooled such that it causes flash freezing of the tissue immediatelysurrounding the area of contact with the drill bit. Freezing of thetissue in this manner may enable an improved ablation pattern and/orreduce pain and bleeding during the procedure.

Exemplary drill bits for any of the above embodiments are a twist bit,hole saw bit, paper drill bit, step drill bit, unibit, lip or spur bit(brad point bit), spade bit, spoon bit, Forstner bit, center bit, augerbit, gimlet bit, installer bit, two-flute bit, three-flute bit, coredrill bit, countersink bit, gun drill bit, microauger, tube with cuttingteeth, and other drill bits known in the art.

Drill bits according to any of the above embodiments of the inventioncan be made from many materials, including metals, metal alloys, shapememory materials, plastics, ceramics, and composite materials such asmetals and metal alloys coated with black oxide, titanium nitride,titanium aluminum nitride, titanium carbon nitride, diamond powder,zirconium nitride, and other hardening agents and combinations of thematerials herein.

Wires and Fibers

The invention further features devices, methods, and apparatuses thatinclude wires (e.g. metallic or non-metallic wires or fibers) or anarray of wires or fibers that can be used to ablate skin in a fractionalpattern.

In one embodiment, a wire is attached to a very thin axle (e.g., aneedle) at one point or at two points to form a loop. The axle has apoint at one end to facilitate insertion into the skin. The other end ofthe axle may be attached to a motor that drives the axle. When the motoris activated, the axle rotates along the longitudinal axis, driving thewire loop at high speed to cut through the skin tissue. The axle canrotate at any useful speed, such as about 500 rpm to about 5000 rpm(e.g., from 500 rpm to 1000 rpm, 500 rpm to 2000 rpm, 500 rpm to 3000rpm, 500 rpm to 4000 rpm, 750 rpm to 1000 rpm, 750 rpm to 2000 rpm, 750rpm to 3000 rpm, 750 rpm to 4000 rpm, 750 rpm to 5000 rpm, 1000 rpm to2000 rpm, 1000 rpm to 3000 rpm, 1000 rpm to 4000 rpm, 1000 rpm to 5000rpm, 1500 rpm to 2000 rpm, 1500 rpm to 3000 rpm, 1500 rpm to 4000 rpm,1500 rpm to 5000 rpm, 2000 rpm to 3000 rpm, 2000 rpm to 4000 rpm, 2000rpm to 5000 rpm, 2500 rpm to 3000 rpm, 2500 rpm to 4000 rpm, or 2500 rpmto 5000 rpm).

In another embodiment, a wire is attached to an axle having the samediameter as the hole to be created. The wire may be attached off-centerand to the outer diameter of the axle. The wire is parallel to the longaxis of the axle. When the axle is rotating at high speed along its longaxis, the wire trajectory defines a cylinder, co-axial with and of thesame diameter as the axle. The wire or fiber may be inserted in the skinwhile the axle is rotating to cut a cylindrical hole. In one embodiment,the wire or fiber is of a fixed shape and length. In other embodiments,the shape and length of the wire may be changed to produce differentablation diameters along the Z axis. Specifically, a larger diameterhole portion may be produced on top of a narrower diameter hole portion.This may be desirable when targeting certain tissues for ablation suchas subdermal fat. A wire or fiber may be fed through a hollow channel inthe penetrating component. The amount of wire fed through thepenetrating component may be adjusted as the component penetrates thetissue. The wire/fiber may also be retracted as the penetratingcomponent is translated through the tissue, thus creating a gradient ofhole diameters along the hole depth. The wire or fiber may be stiff andpossess shape memory, may be flexible, or possess a mixture of the bothrigidity and ductility along the length of the wire or fiber. In someembodiments, the wire or fiber includes preset volumetric contours. Inother embodiments, the wire or fiber includes vertical mire loops (e.g.,to slice away tissue, like potato peeler from the surface across the x-yplane of the skin).

In other embodiments a fiber can be used in place of a wire. Fibers canbe attached at a single point or at dual points along the axis of arotating member. Fibers can be rigid (e.g. a hard plastic such as PEEK)or ductile (e.g., a flexible plastic such as polyethylene). The fibercan be a composite (e.g., glass filled polypropylene) to improve oralter the mechanical properties.

Many types of wires or fibers can be used in the present invention. Forexample, wires can be single stranded, braided, or composites ofindividual wires of a single or multiple gauges or diameters. Wires canhave diameters such that the wire can be attached to a rotatingcomponent and ablate tissue within the desired hole diameter. Forexample, a wire can have a diameter ranging from 30 gauge to 40 gauge(American gauge wire, 255 μm to 80 μm). The diameter of the wire can beless than 80 μm. In some embodiments, the length of the wire can bebetween about 100 μm and about 5000 μm (e.g., 100 μm and 250 μm, 100 μmand 500 μm, 100 μm and 750 μm, 100 μm and 1000 μm, 100 μm and 1500 μm,100 μm and 2000 μm, 100 μm and 2500 μm, 100 μm and 3000 μm, 100 μm and3500 μm, 100 μm and 4000 μm, 100 μm and 4500 μm, 200 μm and 250 μm, 200μm and 500 μm, 200 μm and 750 μm, 200 μm and 1000 μm, 200 μm and 1500μm, 200 μm and 2000 μm, 200 μm and 2500 μm, 200 μm and 3000 μm, 200 μmand 3500 μm, 200 μm and 4000 μm, 200 μm and 4500 μm, 300 μm and 500 μm,300 μm and 750 μm, 300 μm and 1000 μm, 300 μm and 1500 μm, 300 μm and2000 μm, 300 μm and 2500 μm, 300 μm and 3000 μm, 300 μm and 3500 μm, 300μm and 4000 μm, 300 μm and 4500 μm, 400 μm and 500 μm, 400 μm and 750μm, 400 μm and 1000 μm, 400 μm and 1500 μm, 400 μm and 2000 μm, 400 μmand 2500 μm, 400 μm and 3000 μm, 400 μm and 3500 μm, 400 μm and 4000 μm,400 μm and 4500 μm, 500 μm and 750 μm, 500 μm and 1000 μm, 500 μm and1500 μm, 500 μm and 2000 μm, 500 μm and 2500 μm, 500 μm and 3000 μm, 500μm and 3500 μm, 500 μm and 4000 μm, 500 μm and 4500 μm, 600 μm and 750μm, 600 μm and 1000 μm, 600 μm and 1500 μm, 600 μm and 2000 μm, 600 μmand 2500 μm, 600 μm and 3000 μm, 600 μm and 3500 μm, 600 μm and 4000 μm,600 μm and 4500 μm, 700 μm and 750 μm, 700 μm and 1000 μm, 700 μm and1500 μm, 700 μm and 2000 μm, 700 μm and 2500 μm, 700 μm and 3000 μm, 700μm and 3500 μm, 700 μm and 4000 μm, 700 μm and 4500 μm, 800 μm and 1000μm, 800 μm and 1500 μm, 800 μm and 2000 μm, 800 μm and 2500 μm, 800 μmand 3000 μm, 800 μm and 3500 μm, 800 μm and 4000 μm, 800 μm and 4500 μm,900 μm and 1000 μm, 900 μm and 1500 μm, 900 μm and 2000 μm, 900 μm and2500 μm, 900 μm and 3000 μm, 900 μm and 3500 μm, 900 μm and 4000 μm, 900μm and 4500 μm, 1000 μm and 1500 μm, 1000 μm and 2000 μm, 1000 μm and2500 μm, 1000 μm and 3000 μm, 1000 μm and 3500 μm, 1000 μm and 4000 μm,1000 μm and 4500 μm, 1500 μm and 2000 μm, 1500 μm and 2500 μm, 1500 μmand 3000 μm, 1500 μm and 3500 μm, 1500 μm and 4000 μm, 1500 μm and 4500μm, 2000 μm and 2500 μm, 2000 μm and 3000 μm, 2000 μm and 3500 μm, 2000μm and 4000 μm, or 2000 μm and 4500 μm).

Blades

The invention also features blades or an array of blades that may ablateskin in a fractional pattern. In one embodiment, a cylindrical bladehaving the diameter of the hole to be generated may be pushed into theskin to cut a cylindrical hole (e.g., a cylindrical tube with a bladeedge or a micro-coring component). The blade may be rotated to assist inthe tissue ablation. The depth of the hole may be controlled by manuallycontrolling the depth of the blade or by using a depth stop. The ablatedtissue portion inside the cylindrical blade may be removed with a pin,vacuum, positive pressure or other methods described herein.

In another embodiment, straight blade(s) may be used to generate holesthat are not cylindrical. Different patterns of holes may be cutdepending on the geometry and number of blades (e.g. triangle, hexagon,or octagon). Blades may be inserted into the tissues with sufficientforce and speed to produce a desired effect. Alternatively, the bladesmay be oscillated or vibrated at high frequency to enable insertion atlower speed and force (e.g., similar to vibration enhanced commerciallyavailable electric knives and scalpels).

In another embodiment, a plurality of blades is assembled into an arrayto simultaneously cut multiple holes. For example, four blades may beassembled as to generate a blade with a square hole. Several of thesesquare blades may be combined to form an array of blades. The squareblades may be spaced within the array and sized to provide a 5-40% arealremoval of skin once pressed into the tissue and removed. The ablatedtissue portions may be closed with a variety of methods (e.g.,dressings, sutures, closures, and other compressive means). Upon healingthe skin volume will be reduced, thus tightening or reducing the laxityof the skin region.

In another embodiment, the pattern of ablations may be adjusted with avariety of flat cutting blades by changing the pattern of cuts in thetissue. For example, diamond patterns or octagonal patterns may beproduced with a single blade or multiple cutting blades. Ablations ofdesired geometries may be generated by sequential insertion of a singleblade in which the orientation of the blade is changed with respect tothe previous incision.

The removal of the ablated tissue (e.g., the circumscribed tissueregion) may be accomplished with a variety of mechanisms. Mechanicalmeans (e.g., a hook, a scoop, an adhesive), negative pressure (e.g., avacuum), or positive pressure (e.g., fluid or gas pressure) may be usedto remove the ablated tissue portion from the ablation apparatus.

Non-limiting exemplary blades include; taps, cutters, corers, reamers,awls, broaches, step core, pinch, core, rotary, and punches. Exemplaryblade materials include: metal (e.g., a stainless steel tube, 304stainless steel, a surgical stainless steel), metal alloys, polymer orplastic, glass, ceramics, or other structural materials. Blades may be acomposite of one or more materials including: metals and metal alloyscoated with black oxide, titanium nitride, titanium aluminum nitride,titanium carbon nitride, diamond powder, zirconium nitride, and otherhardening agents and combinations of materials such as polymers,plastics, ceramics and other structural materials. Additional exemplarycoatings include a lubricant, a low-friction material (e.g., Teflon™), achromium coating (e.g., ME-92™, such as to increase material strength),a plastic, a polymer (e.g., nylon or polyethylene), a polished metalalloy, or the like.

Further, the tubes, blades, pins, and ablation apparatuses can be formedfrom any useful material and optionally coated or chemically treated topromote incision or excision of a tissue portion and/or to increaseprecision or effectiveness for treating the skin region. Exemplarymaterials include metal, a biopsy needle, an epoxy, a glass, a polymer,a plastic, a resin, another structurally rigid material, or a similarstructure.

High Pressure Fluid Jet

In other embodiments, the invention features high pressure fluid jets oran array of high pressure fluid jets that may ablate skin in afractional pattern.

In one embodiment, an ablation apparatus containing at least one highpressure fluid jet (e.g., fluid pressure of greater than 1380 kPa or 200psi) may be positioned external to the skin surface. The high pressurefluid jet is applied to the skin surface, thus producing a hole. Thesize of the hole may be determined by the fluid jet size and length ofexposure. For example, to provide an ablated skin portion with ashallower depth, the fluid jet may be applied for a shorter time.Alternatively, to provide an ablated skin portion with a greater depthor diameter, the fluid jet may be applied to the skin region for alonger time. A high pressure fluid jet is a non-thermal ablativemechanism and does not generate a thermal injury to the surroundingtissue. An exemplary method for removing excess fluid, tissue or debrisgenerated during ablation is using a vacuum source (negative pressure)or a pressurized air stream (positive pressure).

Exemplary non-limiting pressures include from about 200 psi to about100000 psi (e.g., from 200 psi to 1000 psi, 200 psi to 5000 psi, 200 psito 10000 psi, 200 psi to 50000 psi, 500 psi to 1000 psi, 500 psi to 5000psi, 500 psi to 10000 psi, 500 psi to 50000 psi, 500 psi to 100000 psi,750 psi to 1000 psi, 750 psi to 5000 psi, 750 psi to 10000 psi, 750 psito 50000 psi, 750 psi to 100000 psi, 1000 psi to 5000 psi, 1000 psi to10000 psi, 1000 psi to 50000 psi, 1000 psi to 100000 psi, 1500 psi to5000 psi, 1500 psi to 10000 psi, 1500 psi to 50000 psi, 1500 psi to100000 psi, 2000 psi to 5000 psi, 2000 psi to 10000 psi, 2000 psi to50000 psi, 2000 psi to 100000 psi, 2500 psi to 5000 psi, 2500 psi to10000 psi, 2500 psi to 50000 psi, 2500 psi to 100000 psi, 4000 psi to5000 psi, 4000 psi to 10000 psi, 4000 psi to 50000 psi, 4000 psi to100000 psi, 5000 psi to 10000 psi, 5000 psi to 50000 psi, 5000 psi to100000 psi, 7500 psi to 10000 psi, 7500 psi to 50000 psi, 7500 psi to100000 psi, 10000 psi to 50000 psi, 10000 psi to 100000 psi, 50000 psito 100000 psi, or 75000 psi to 100000 psi).

In another embodiment, an ablation apparatus containing fluid jets isinserted in the fatty layer, under the dermis and epidermis. The arrayof high pressure fluid jets emits fluid at very high pressure to ablatethe tissue above. A low pressure out-flow tube may be positioned on thesurface of the skin to remove fluid and debris. In another embodiment, adiscontinuous fluid flow may be used to allow removal of fluid anddebris before reactivating the high-pressure jet. In another embodiment,the jet array can be moved (e.g., in a circular fashion) in relation tothe skin so as to produce an array of cylindrical ablations.

High pressure fluid jets of the invention may be a coherent fluid streamor an incoherent fluid stream. One or more nozzles may be used to formthe fluid jet. For example, a convergent nozzle may be used whichreduces the diameter of the outlet, thus increasing the velocity of thefluid jet.

Many fluids may be used to make the high pressure fluid jet.Non-limiting examples include: aqueous and non aqueous solutions, suchas isotonic and non isotonic buffers, and saline solutions, and mayinclude additional ingredients that have a desirable medical oraesthetic activity or utility. Exemplary additional therapeutic agentsinclude but are not limited to heparin, fibrin, antibiotics, lidocaineand other analgesics.

Cryosurgery

Tissue ablation according to the invention may also be accomplished bycryosurgery, in which extreme cold is used to destroy tissue.Cryosurgery is a less invasive alternative to surgery; and generally hasless complications and side effects. Cold temperature is typicallygenerated with a cryogen, such as liquid nitrogen (−196 degrees C.),carbon dioxide (−78.5 degrees C.), argon gas (−185.5 degrees C.), and/ordimethyl ether-propane (−41 degrees C.), or cold probes.

Ablation of tissue in a fractional pattern may be achieved bycryosurgery. Ablated columns of tissue resorb and are replaced byhealthy tissue. This fractional ablation technology is less invasivethan fractional surgical ablation. This results in faster healing andmay limit side effects and other complications (e.g., no bleeding, lowerrisk of infection). Following fractional cryosurgery, a compressivewound dressing may be applied to the skin to enhance skin tightening.

In one embodiment an array of miniature cold probes is applied to a skinregion. The probes locally decrease the skin temperature, thus freezingand destroying and/or ablating the tissue at the skin region surface.The resulting ablation is superficial (e.g., only at the skin surface)which provides ablated tissue portions with high width to depth ratios.Therefore, this technique is well suited to improvement of skin textureand color.

In another embodiment, cold needles are inserted into the skin region.This embodiment allows ablation of deep skin tissue. One may envisionthe formation of full depth skin ablations (i.e. ablation of theepidermis and dermis layer). Ablated tissue portions spanning both theepidermis and dermis layers of the skin are best suited for skintightening. To maximize the skin tightening treatment, the ablation isfollowed by a compressive wound dressing. The penetrating components maybe temperature controlled and may consist of a temperature conductivematerial. The temperature conductive material may be brought intoproximity with a heat sink. Given the small size of the penetratingcomponents, such cooling may occur within seconds or sub-secondtimeframes. Such temperature conductive materials include metals such ascopper and stainless steel.

In another embodiment, penetrating components may be fashioned toinclude regions composed of temperature non-conductive (e.g., insulator)materials to help shield regions of the tissue or imbed patterns intothe tissue from exposure to extremes of temperature. For example, acryoneedle can be coated with an insulating material on only one side,thus leaving the other side of the needle thermally conducting. Afterreducing the temperature of the cryoneedle with a heat sink, thethermally conductive side will freeze tissue while the sides coated withan insulator will not, thus forming asymmetric hole diameters (e.g.non-circular).

Needles can be cooled by any useful process. In one non-limitingexample, one can envision attaching the needles to a Peltier cell (heatpump) that cools the needles, while the other side of the Pelletier cellis heated and heat is dissipated through radiators. In anothernon-limiting example, a cooling fluid may be circulated in the needle(e.g., the apparatus can include an internal needle and an externalneedle, where the internal needle includes a first material havingconductive properties (e.g., a metal, such as any described herein) andincludes a cryogen within the lumen of the internal needle, therebycooling the external needle). In other embodiments, the external needleincludes a second material on its distal end (e.g., silver). In yetanother non-limiting example, the needle may be used as amicro-evaporator in a refrigerating circuit.

Chemical or Bioactive Agents

In another embodiment, chemical or bioactive agents may also be used todestroy or ablate skin tissue. Typical chemical or bioactive agents usedinclude trichloracetic acid, alpha hydroxy acids, beta hydroxy acids,liquid nitrogen, hypoosmotic fluids, hyperosmotic fluids, and bioactiveproteins (e.g., one or more hormones, antibodies, and/or enzymes, suchas enzymes that liquefy tissue, such as one or more proteases, DNases,hyaluronidase, and collagenases, or combinations thereof). Chemicals orbioactive agents are used to create an injury, ablated tissue portion,and/or stimulate new tissue formation.

In one embodiment, tissue may be denatured, ablated, and/or destroyed ina fractional pattern with chemical or bioactive agents. For example, anarray of needles with side-holes along the needle body may be introducedin the skin. The multiple side-holes in the needles allows for injectionof a chemical or bioactive denaturizing agent at multiple depths,allowing for full-thickness denaturation of columns of skin tissue.

In another embodiment, the needle side-holes can be configured to supplya chemical or bioactive agent to specific areas along the needle or in aspecific pattern. In addition, the size of the needle side holes maycontrol the amount of chemical or bioactive agent delivered to aparticular location. This embodiment allows for the formation of ablatedtissue portions with multiple diameters along the length, asymmetricstructures, and serrated cross-sectional dimension.

Microelectrodes

In yet another embodiment, ablation may be accomplished by non-thermalirreversible electroporation, which involves the application of veryshort bursts of electricity (microsecond duration range) at a specificvoltage and frequency to form nanopores in the cell membrane. Theelectroporation parameters may be selected to form reversible pores(i.e., the cell may repair and restore normal function) or irreversiblepores (i.e., the treatment produces cell apoptosis). The electroporationmay be configured to use a set of parameters such that the energy onlyaffects targeted tissue. For example, a specific cell type may bedestroyed without affecting an extracellular matrix, nerves, or bloodvessels. Small electrodes (diameter in the mm range) are typically usedfor electroporation.

In one embodiment, a non-thermal irreversible electroporation may beused for fractional skin region or tissue ablation. Carefully selectedtreatment parameters limit the effect of the electroporation to the skinregion, thus leaving blood vessels and nerve fibers substantiallyunaffected and without significant heating of the surrounding tissue.For example, a pair of needle electrodes may be inserted into a skinregion. A first electrode of the electrode pair may be an activeelectrode and the second electrode of the pair may be a returnelectrode. The ablated tissue portion occurs in the tissue volumebetween the electrode pair. The electrical parameters (e.g., thevoltage, current and power) between the active and return electrode maybe selected to affect only the desired tissue and provide ablation in aspecific location.

In another embodiment, the electrodes may be configured to affect onlycells in the dermal layer while leaving the epidermal cells unaffected.The electrode or electrode pair may be located only at the tip of theneedle (e.g., the upper portion of the needle is not conductive). Inthis embodiment, the electroporation between the electrode pair onlyoccurs in the dermal layer, thus providing selective ablation of thedermis.

Another embodiment for irreversible electroporation includes insertionof an array of needles into a skin region. The needles are connected toa generator that emits pulses of electricity of pre-selected duration,frequency, and intensity. The array includes pairs of electrodes, eachhaving an active electrode and a return electrode located in closeproximity to generate a pulsed and high intensity electrical fieldbetween the pairs of electrodes. The electrical field leads tonon-thermal, irreversible electroporation of the tissue located betweenelectrode pairs. The treatment parameters are selected as to onlygenerate apoptosis of skin cells. In a further embodiment, the electrodepairs can be positioned in a non-parallel configuration, thus producingablated tissue portions with varied geometry, diameters, and serratedcross-sectional dimensions.

In another embodiment, a probe or needle containing multiple electrodes(e.g., each having an active and a return electrode pair) may be used toform bi-polar electrodes for the electroporation of tissue. Bi-polarelectrodes consist of two conductive surfaces separated by an electricalinsulator. One conductive surface acts as an active electrode while theother surface acts as a return electrode. Ablated tissue portions can beformed around the bi-polar electrode as the electrical energy movesthrough the tissue adjacent to the bi-polar electrode. In a furtherembodiment, the bi-polar electrode may have different shapes orgeometric configurations, thus producing ablated tissue portions withvaried geometry, diameters, and serrated cross-sectional dimensions. Inother embodiments, the electrodes may be monopolar.

Exemplary conductive materials include metals (e.g., copper andaluminum), metal alloys, electrolyte gels, and conductive polymers.Exemplary insulator materials include polyvinylchloride (PVC), glass,polytetrafluoroethylene (PTFE), and ceramics.

The microelectrodes, probes, and needles can be have useful voltage,amperage, and/or frequency. The electric field generated on the skin canbe, e.g., from about 500 V/cm to 5000 V/cm (e.g., from 500 V/cm to 1000V/cm, 500 V/cm to 2000 V/cm, 500 V/cm to 3000 V/cm, 500 V/cm to 4000V/cm, 600 V/cm to 1000 V/cm, 600 V/cm to 2000 V/cm, 600 V/cm to 3000V/cm, 600 V/cm to 4000 V/cm, 600 V/cm to 5000 V/cm, 700 V/cm to 1000V/cm, 700 V/cm to 2000 V/cm, 700 V/cm to 3000 V/cm, 700 V/cm to 4000V/cm, 700 V/cm to 5000 V/cm, 800 V/cm to 1000 V/cm, 800 V/cm to 2000V/cm, 800 V/cm to 3000 V/cm, 800 V/cm to 4000 V/cm, 800 V/cm to 5000V/cm, 900 V/cm to 1000 V/cm, 900 V/cm to 2000 V/cm, 900 V/cm to 3000V/cm, 900 V/cm to 4000 V/cm, or 900 V/cm to 5000 V/cm).

In addition, the voltage-loaded area average electric field can bebetween, e.g., about 5 V/cm to about 900 V/cm (e.g., from 5 V/cm to 100V/cm, 5 V/cm to 200 V/cm, 5 V/cm to 300 V/cm, 5 V/cm to 400 V/cm, 5 V/cmto 500 V/cm, 5 V/cm to 600 V/cm, 5 V/cm to 700 V/cm, 5 V/cm to 800 V/cm,10 V/cm to 100 V/cm, 10 V/cm to 200 V/cm, 10 V/cm to 300 V/cm, 10 V/cmto 400 V/cm, 10 V/cm to 500 V/cm, 10 V/cm to 600 V/cm, 10 V/cm to 700V/cm, 10 V/cm to 800 V/cm, 10 V/cm to 900 V/cm, 15 V/cm to 100 V/cm, 15V/cm to 200 V/cm, 15 V/cm to 300 V/cm, 15 V/cm to 400 V/cm, 15 V/cm to500 V/cm, 15 V/cm to 600 V/cm, 15 V/cm to 700 V/cm, 15 V/cm to 800 V/cm,15 V/cm to 900 V/cm, 25 V/cm to 100 V/cm, 25 V/cm to 200 V/cm, 25 V/cmto 300 V/cm, 25 V/cm to 400 V/cm, 25 V/cm to 500 V/cm, 25 V/cm to 600V/cm, 25 V/cm to 700 V/cm, 25 V/cm to 800 V/cm, 25 V/cm to 900 V/cm, 50V/cm to 100 V/cm, 50 V/cm to 200 V/cm, 50 V/cm to 300 V/cm, 50 V/cm to400 V/cm, 50 V/cm to 500 V/cm, 50 V/cm to 600 V/cm, 50 V/cm to 700 V/cm,50 V/cm to 800 V/cm, 50 V/cm to 900 V/cm, 75 V/cm to 100 V/cm, 75 V/cmto 200 V/cm, 75 V/cm to 300 V/cm, 75 V/cm to 400 V/cm, 75 V/cm to 500V/cm, 75 V/cm to 600 V/cm, 75 V/cm to 700 V/cm, 75 V/cm to 800 V/cm, or75 V/cm to 900 V/cm).

The voltage (e.g., RF voltage in pulse or continuous mode) can be fromabout 10 V_(RMS) to about 200 V_(RMS) (e.g., 10 V_(RMS) to 50 V_(RMS),10 V_(RMS) to 100 V_(RMS), 10 V_(RMS) to 150 V_(RMS), 15 V_(RMS) to 50V_(RMS), 15 V_(RMS) to 100 V_(RMS), 15 V_(RMS) to 150 V_(RMS), 15V_(RMS) to 200 V_(RMS), 20 V_(RMS) to 50 V_(RMS), 20 V_(RMS) to 100V_(RMS), 20 V_(RMS) to 150 V_(RMS), 20 V_(RMS) to 200 V_(RMS), 30V_(RMS) to 50 V_(RMS), 30 V_(RMS) to 100 V_(RMS), 30 V_(RMS) to 150V_(RMS), 30 V_(RMS) to 200 V_(RMS), 40 V_(RMS) to 50 V_(RMS), 40 V_(RMS)to 100 V_(RMS), 40 V_(RMS) to 150 V_(RMS), or 40 V_(RMS) to 200 V_(Rms))In some non-limiting embodiments, the load voltage can be from about 300V to about 600 V. In other embodiments, the applied voltage is fromabout 100 V to about 2000 V (e.g., from 100 V to 500 V, 100 V to 1000 V,100 V to 1500 V, 250 V to 500 V, 250 V to 1000 V, 250 V to 1500 V, 250 Vto 2000 V, 500 V to 1000 V, 500 V to 1500 V, 500 V to 2000 V, 750 V to1000 V, 750 V to 1500 V, or 750 V to 2000 V). In general, high-voltage(e.g., more than about 150V) results in electroporation of skin.Furthermore, transdermal voltage for electroporation can be temperaturedependent. For the non-limiting example of human stratum corneum,electroporation occurs at a transdermal voltage difference of 80V<Uskin<100 V at 4° C. or 10 V<Uskin<20 V at 60° C. (see, e.g., Pliquettet al., J Theor Biol. 2008 Mar. 21; 251(2): 195-201).

Further, voltage can be provided in pulse or continuous mode.Non-limiting exemplary protocols include (i) 10 pulses of 1000 V(applied voltage) of 100 ms duration (10×1000 V-100 ms) and (ii) 10pulses of 335 V, each with a duration of 5 ms.

Current (e.g., DC or AC) can be of any amplitude that allows forablation. Non-limiting exemplary ranges include from about 0.1 A to 5 A,from about 10 mA to 500 mA, or from about 100 μA to about 1000 μA. Ingeneral, small electrical currents (e.g., more than about 0.4 mA/cm²)results in iontophoresis across the skin. The frequency of the appliedcurrent (e.g., DC or AC) can be of any useful range, such as from about1 Hz to 1000 Hz (e.g., for DC). For AC, the frequency can be, e.g., fromabout 100 kHz to about 250 kHz.

Further voltage, current, and frequency ranges are described in U.S.Pat. Nos. 5,885,211 and 8,209,006; EP 0027974; EP 1224949 A1; EP 2409727A1; WO 2012052986; Dujardin et al., J Control Release. 2002 Feb. 19;79(1-3):219-27; Cevc, Expert Opin Investig Drugs. 1997 December;6(12):1887-937; Pliquett et al., J Theor Biol. 2008 Mar. 21; 251(2):195-201; and Prausnitz et al., Proc Natl Acad Sci USA. 1993 Nov. 15;90(22): 10504-10508, each of which is incorporated in its entirety byreference.

Femtosecond Lasers

Femtosecond lasers (e.g., an excimer laser) also allow for non-thermalablation of tissue. High intensity femtosecond pulses induce non-linearmultiphoton absorption, generating free electron emission. As a result,the surface becomes positively charged. An intense electrical fieldresults in the distribution of negative and positive charges and pullspositive ions out of the surface (Coulomb explosion). The localtemperature rise is negligible.

In one embodiment, a femtosecond laser may be used to ablate a tissueportion from a skin region. The ablation depth of femtosecond lasers isin the nanometer to micrometer range for a pulse train. This allows forvery accurate control of the total ablation depth. Therefore, theablation occurs slowly with each pulse, forming an ablated tissueportion with highly controlled dimensions. The femtosecond laserprovides non-thermal ablation and does not transfer thermal energy tothe surrounding tissue. The tissue may be compressed to improve healingand tighten the skin using methods similar to methods used forsurgically excised tissue.

The laser can have any useful parameter for ablation, includingwavelength, pulse energy, intensity, or pulse duration. Exemplarynon-limiting lasers and related wavelengths (in nm) include argon(488-514 nm), intense pulse light (500-1200 nm), dye (540 nm or 570-640nm), copper (510 or 578 nm), krypton (416, 531, 568, 752, or 800 nm),KTP/diode (532 nm), diode (800, 940, 980, or 1450 nm, such as DPSS(diode pumped solid state)), Nd:YAG (1064, 1320, 1440, or 1550 nm),Nd:YVO₄ (1064 nm), Nd:YLF (1047 or 1053 nm), Er:YAG (1550 or 2940 nm),Er:glass (1540 nm), thulium (1927 nm), Er:YSGG (2780 nm), holmium (2100nm), CO₂ (10600 nm), ruby (694 nm), and alexandrite (755 nm), as well ascombinations thereof. In some embodiments, the beam of radiation canhave a wavelength from about 380 nm to about 2600 nm (e.g., from 1200 nmto 2600 nm, from 1200 nm to 1800 nm, or from 1300 nm to 1600 nm). Inother embodiments, the beam of radiation can have a wavelength of about1500 nm, 2100 nm, or 2200 nm. In yet other embodiments, the laser is anexcimer laser (e.g., an excimer of any one of the following moleculesand associated wavelength: Ar₂ (126 nm), Kr₂ (146 nm), Xe₂ (172 and 175nm), ArF (193 nm), KrF (248 nm), XeBr (282 nm), XeCl (308 nm), XeF (351nm), or KrCl (222 nm)).

In various non-limiting embodiments, a particular penetration depth oflight into the skin (and a corresponding depth of ablation) can betargeted by selecting a wavelength of a beam of radiation. For example,a water absorption coefficient [μa] can be taken from G. M. Hale and M.R. Querry, “Optical constants of water in the 200 nm to 200 μmwavelength region,” Appl. Opt., 12, 555-563, (1973) and an OpticalPenetration Depth (OPD) can be calculated using a diffusionapproximation. The pa of skin is taken as pa of water multiplied by 0.7,and the product of scattering coefficient is taken as 12 cm⁻¹. Exemplarywavelengths (in nm) and related optical penetration depths (in mm)include, without limitation, 1180 nm (1.9 mm), 1240 nm (2.07 mm), 1300nm (1.83 mm), 1340 nm (1.40 mm), 1360 nm (1.11 mm), 1400 (0.43 mm), 1540nm (0.45 mm), 1640 nm (0.79 mm), 1780 nm (0.58 mm), 1880 nm (0.21 mm),2360 nm (0.18 mm), or 2600 nm (0.05 mm).

Exemplary pulse durations include from about 1 fs and 400 ns (e.g.,using Q-switched short pulsed Nd:YAG laser) or from about 0.1 ms toabout 500 ms (e.g., millisecond long pulsed Nd:YAG laser energy).Exemplary fluence (or intensity) includes from about 0.1 J/cm² to about300 J/cm² (e.g., from 0.1 J/cm² to 5 J/cm², 0.1 J/cm² to 10 J/cm², 0.1J/cm² to 25 J/cm², 0.1 J/cm² to 50 J/cm², 0.1 J/cm² to 100 J/cm², 0.1J/cm² to 150 J/cm², 0.1 J/cm² to 200 J/cm², 0.1 J/cm² to 250 J/cm², 0.5J/cm² to 5 J/cm², 0.5 J/cm² to 10 J/cm², 0.5 J/cm² to 25 J/cm², 0.5J/cm² to 50 J/cm², 0.5 J/cm² to 100 J/cm², 0.5 J/cm² to 150 J/cm², 0.5J/cm² to 200 J/cm², 0.5 J/cm² to 250 J/cm², 0.5 J/cm² to 300 J/cm², 1J/cm² to 5 J/cm², 1 J/cm² to 10 J/cm², 1 J/cm² to 25 J/cm², 1 J/cm² to50 J/cm², 1 J/cm² to 100 J/cm², 1 J/cm² to 150 J/cm², 1 J/cm² to 200J/cm², 1 J/cm² to 250 J/cm², 1 J/cm² to 300 J/cm², 1.5 J/cm² to 5 J/cm²,1.5 J/cm² to 10 J/cm², 1.5 J/cm² to 25 J/cm², 1.5 J/cm² to 50 J/cm², 1.5J/cm² to 100 J/cm², 1.5 J/cm² to 150 J/cm², 1.5 J/cm² to 200 J/cm², 1.5J/cm² to 250 J/cm², 1.5 J/cm² to 300 J/cm², 2 J/cm² to 5 J/cm², 2 J/cm²to 10 J/cm², 2 J/cm² to 25 J/cm², 2 J/cm² to 50 J/cm², 2 J/cm² to 100J/cm², 2 J/cm² to 150 J/cm², 2 J/cm² to 200 J/cm², 2 J/cm² to 250 J/cm²,2 J/cm² to 300 J/cm², 3 J/cm² to 5 J/cm², 3 J/cm² to 10 J/cm², 3 J/cm²to 25 J/cm², 3 J/cm² to 50 J/cm², 3 J/cm² to 100 J/cm², 3 J/cm² to 150J/cm², 3 J/cm² to 200 J/cm², 3 J/cm² to 250 J/cm², 3 J/cm² to 300 J/cm²,5 J/cm² to 10 J/cm², 5 J/cm² to 25 J/cm², 5 J/cm² to 50 J/cm², 5 J/cm²to 100 J/cm², 5 J/cm² to 150 J/cm², 5 J/cm² to 200 J/cm², 5 J/cm² to 250J/cm², or 5 J/cm² to 300 J/cm²). As wavelength between about 380 nm andabout 2600 nm is absorbed by water and skin is about 70% water, theabsorption coefficient of skin can be approximated as 70% of theabsorption coefficient of water. Further, as the absorption coefficientof water is a function of the wavelength of radiation, the desiredfluence depends on the chosen wavelength of radiation, as can bedetermined by a skilled artisan. For example, for short pulses ofradiation, the fluence can be, e.g., in a range of between about 0.1J/cm² to about 10 J/cm², and more preferably between about 1.5 J/cm² toabout 5 J/cm².

The pulse energy can be, e.g., from about 0.01 J to about 5 J (e.g.,from 0.01 J to 0.05 J, 0.01 J to 0.1 J, 0.01 J to 0.5 J, 0.01 J to 1 J,0.01 J to 2 J, 0.01 J to 3 J, 0.01 J to 4 J, 0.05 J to 0.1 J, 0.05 J to0.5 J, 0.05 J to 1 J, 0.05 J to 2 J, 0.05 J to 3 J, 0.05 J to 4 J, 0.05J to 5 J, 0.1 J to 0.5 J, 0.1 J to 1 J, 0.1 J to 2 J, 0.1 J to 3 J, 0.1J to 4 J, 0.1 J to 5 J, 0.5 J to 1 J, 0.5 J to 2 J, 0.5 J to 3 J, 0.5 Jto 4 J, 0.5 J to 5 J, 1 J to 2 J, 1 J to 3 J, 1 J to 4 J, 1 J to 5 J,1.5 J to 2 J, 1.5 J to 3 J, 1.5 J to 4 J, or 1.5 J to 5 J). In otherembodiments, about 12 J of energy is delivered to a skin section of 0.8cm² in one second.

Non-limiting exemplary protocols include the following: a pulse durationof about 10 ns, pulse energy of 1.2 J, beam cross sectional area ofabout 0.8 cm², and repetition rate of about 1-10 Hz for an alexandritelaser (755 nm with a beam cross sectional area of about 0.5 cm²); apulse duration of about 10 ns, a beam diameter of about 10 mm, and abeam pulse fluence of about 2 J/cm²; a 10 mm diameter beam at a beampulse energy density, or fluence, of about 1 J/cm², using a 10 ns pulseat a frequency of 10 pulses per minute with a ruby laser (694 nm); abeam diameter of about 8-12 mm (e.g., about 8 mm), fluence of about 0.1J/cm² to about 10 J/cm² (e.g., about 3 J/cm²), pulse duration of about 5ns to about 50 ns (e.g., about 10 ns) with a Q-switched Nd:YAG laser(1064 nm); light with wavelengths of between about 400 nm and about 1500nm (e.g., between about 600 nm and about 1300 nm) having a pulseduration between about 100 μs and about 200 ms (e.g., in the range ofabout 10 ms to about 100 ms) and a beam diameter of about 8 mm to about12 mm; a titanium sapphire near-infrared laser (e.g., a CoherentRadiation Mira Titanium Sapphire mode-locked laser) emitting 200 fsecpulses with a 76 MHz repetition rate, which can be pumped by an argonion laser operated at 12 watts in a multi-line mode, where optionally,the method of pumping a pulsed laser could be performed according to anyof the generally accepted methodologies, including but not limited to,single or multi-line optical pumping, electrical pumping or chemicalpumping; a laser having an operating wavelength of 780 nm using a beamscanning system used in confocal microscopy over a tissue region (95μm²) having a dwell time of tens of microseconds at each of theapproximately 250,000 pixels in the scan (the entire scan time being5-20 seconds) and power between 10 to 30 mwatts (e.g., about 20 mwatts);a pulse duration of about 10 to 30 ns a pulse repetition rate betweenabout 8 and 100 Hz with an excimer laser (e.g., having power between 20and 100 mW); or a pulse duration of about 100 ms, a beam cross sectionof 0.8 cm², a repetition rate of up to about 5 HZ, and a pulse intensityor fluence of about 80 J/cm² with a long pulse alexandrite laser (755nm), where each protocol can optionally include a layer of particles(e.g., carbon particles) on the skin. Exemplary protocols and parametersare described in U.S. Pub. No. 20120253333; U.S. Pat. Nos. 8,435,791 and8,246,611; WO 2012135828; and WO 1999029243, each of which isincorporated by reference in its entirety.

Direct Vacuum Ablation

In yet another embodiment of the invention, penetrating components thatare joined to a source of an extremely high vacuum may be brought intocontact with a tissue. The high level of vacuum is sufficient to removetissue through either a suctioning mechanism or through conveyance ofdamage to the tissue that is targeted for removal or destruction. In oneembodiment, a hollow coring needle or another penetrating component,configured to connect an external tissue portion to the vacuum inside(e.g., a hollow coring needle or a needle with side-holes or slots,thereby allowing for connection tissue along the long axis of theneedle), may be inserted into a skin region. A vacuum is applied (e.g.,a vacuum with an absolute pressure less than about 6.3 kPa or any rangesdescribed herein), and tissue adjacent to the needle is damaged by thevacuum. The size of an ablated tissue portion may be controlled by thelevel of vacuum and the duration of exposure. In one embodiment, vacuumcan ablate tissue by causing local boiling off or vaporization of tissueat ambient temperatures. In another embodiment, vacuum can ablate tissueby causing desiccation or freeze-drying of tissue.

Ultrasound Ablation

In yet another embodiment of the invention, penetrating components thatare joined to a source of a high intensity ultrasound wave may be boughtinto contact with a tissue. The high intensity of ultrasound waveconducts vibrational energy, which is sufficient to cause cellular andtissue disruption. In one embodiment, a needle or another penetratingcomponent configured to connect to an external tissue portion to theultrasound wave may be inserted into a skin region. An ultrasound waveis applied (e.g., an ultrasound wave with a frequency greater than about20 kHz) and tissue, either in direct contact with the needle or inproximity of the needle, is damaged by the ultrasound wave. The size ofan ablated tissue portion may be controlled by the intensity ofultrasound wave and the duration of exposure. In one embodiment,ultrasound can ablate tissue by causing liquefaction of the tissue.Liquefied tissue may be removed either by squeezing the tissue or byusing an absorbent tool or material (e.g., a straw).

Ablation Apparatus Arrays

The ablation apparatuses described herein may be assembled into arraysof ablation apparatuses to facilitate skin treatment over larger areasand in less time. An array may contain a homogeneous set of ablationapparatuses (e.g., all the apparatuses are identical square blades) orthe array may contain a heterogeneous array of ablation apparatuses(e.g., a mixture of blade geometries or a mixture of cryoprobes andblades). The ablation apparatus array may include one or more tissueremoval apparatuses or tissue positioning apparatuses. The ablationapparatus array may be included in a device which allows for an improveduser interface, including sensors, therapeutic agents, guides, andsanitizing/cleaning features.

The apparatuses for making ablations (e.g., drill, blades, probe and/ortubes) can be provided in any useful arrangement (e.g., a linear array,a radial array, or any described herein) of one or more components(e.g., two, three, four, five, ten, thirty, fifty, hundred, or more).The spacing between each ablation apparatus (e.g., drill, blade and/ortube) can be of any useful dimension, such as between about 0.5 mm and50 mm (e.g., between about 1 mm and 40 mm, 1 mm and 30 mm, 1 mm and 25mm, 1 mm and 20 mm, 1 mm and 15 mm, 1 mm and 10 mm, 1 mm and 5 mm, 1 mmand 3 mm, 3 mm and 50 mm, 3 mm and 40 mm, 3 mm and 30 mm, 3 mm and 25mm, 3 mm and 20 mm, 3 mm and 15 mm, 3 mm and 10 mm, 3 mm and 5 mm, 5 mmand 50 mm, 5 mm and 40 mm, 5 mm and 30 mm, 5 mm and 25 mm, 5 mm and 20mm, 5 mm and 15 mm, 5 mm and 10 mm, 10 mm and 50 mm, 10 mm and 40 mm, 10mm and 30 mm, 10 mm and 25 mm, 10 mm and 20 mm, 10 mm and 15 mm, 15 mmand 50 mm, 15 mm and 40 mm, 15 mm and 30 mm, 15 mm and 25 mm, 15 mm and20 mm, 20 mm and 50 mm, 20 mm and 40 mm, 20 mm and 30 mm, 20 mm and 25mm, 30 mm and 50 mm, 30 mm and 40 mm, or 40 mm and 50 mm).

Such arrangements can include one or more ablation apparatuses (e.g.,about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75,100, or more ablation apparatuses, such as between about 2 and 100ablation apparatuses (e.g., between 2 and 10, 2 and 15, 2 and 20, 2 and25, 2 and 30, 2 and 35, 2 and 40, 2 and 45, 2 and 50, 2 and 75, 5 and10, 5 and 15, 5 and 20, 5 and 25, 5 and 30, 5 and 35, 5 and 40, 5 and45, 5 and 50, 5 and 75, 5 and 100, 10 and 20, 10 and 25, 10 and 30, 10and 35, 10 and 40, 10 and 45, 10 and 50, 10 and 75, 10 and 100, 15 and20, 15 and 25, 15 and 30, 15 and 35, 15 and 40, 15 and 45, 15 and 50, 15and 75, 15 and 100, 20 and 25, 20 and 30, 20 and 35, 20 and 40, 20 and45, 20 and 50, 20 and 75, 20 and 100, 25 and 30, 25 and 35, 25 and 40,25 and 45, 25 and 50, 25 and 75, 25 and 100, 30 and 35, 30 and 40, 30and 45, 30 and 50, 30 and 75, 30 and 100, 35 and 40, 35 and 45, 35 and50, 35 and 75, 35 and 100, 40 and 45, 40 and 50, 40 and 75, 40 and 100,50 and 75, or 50 and 100)).

Such arrangements of ablation apparatuses can be any of varioustwo-dimensional or three-dimensional patterns along a base holding oneor more components for making ablations (e.g., blades and/or tubes). Thebase can be optionally mounted on a roller apparatus having acylindrical body with a longitudinal rotational axis, where the one ormore blades and/or tubes are arranged on the longitudinal surface of thecylindrical body. In some embodiments, the blade or tube extends assubstantially coplanar extensions of the cylindrical body. In use,rotation of the cylindrical body along the skin results in the ablationof tissue portions by the ablation apparatuses. Exemplary rollerapparatuses are provided in FIGS. 11A-11B and its associated text inU.S. Pub. No. 2011/0251602, in FIGS. 3A-3B and its associated text inInternational Pub. No. WO 2012/103492, which are hereby incorporated byreference in its entirety.

Additional Components

Any of the devices, apparatuses, and methods herein can be integratedwith other useful components. For instance, an ablation apparatusincluding a drill bit could benefit from use with a cryosource, such asto cool the skin prior to drilling. Accordingly, this ablation apparatuscan include a cryosource, such as any described herein. In a similarmanner, any of the apparatuses herein (e.g., an ablation apparatus) caninclude one or more of a cryosource, a vacuum, a motor, a generator, aninsulator, and/or a sensor.

Another additional component is an alignment feature. In devices of theinvention that combine an ablation apparatus with a tissue removal ortissue positioning apparatus, an aligning feature may provide a means toensure the ablated tissue portion is removed correctly (e.g., the tissueremoval apparatus is aligned with the ablated tissue portions) or toensure the skin region is flat prior to ablation (e.g., the tissuepositioning apparatus holds the skin region in a flat position undertension).

Removal Apparatuses and Methods for Removing Tissue

Mechanical or Physical Methods

An ablated tissue portion may require removal from a skin region or anablation apparatus of the invention. For example, an ablated tissueportion may be captured in a hollow micro-coring needle, a micro-coringpaper drill, a micro-coring hole saw, or a micro-coring blade array.After capture, the ablation apparatus (e.g., the hollow micro-coringneedle, micro-coring paper drill, micro-coring hole saw, or micro-coringblade array) may be removed from the skin region, but the ablated tissueportion still lodged inside the ablation apparatus. The ablated tissueportion needs to be removed in order to continue the skin treatmentprocedure. In one embodiment, a pin may be inserted from one side to theablation apparatus and used to push out the ablated tissue portion. Inanother embodiment, the tissue may be pushed out using compressed air ora pressurized fluid.

In another embodiment, a separate tool may be used to remove the ablatedtissue portion from the skin region. For example, micro-tweezers may beused to pull tissue out of an ablated tissue portion or hole. In anotherembodiment, the tissue removal apparatus may be configured with asurface that adheres to the ablated tissue. When the tissue removalapparatus is removed, the ablated tissue is pulled out of the holes. Inone embodiment, the removal apparatus is configured with a flexiblesupport layer attached to an adhesive layer (e.g., tape). The apparatusis applied on the skin region. The tissue removal device adheres to theablated tissue as well as to the surrounding skin region. When thetissue removal apparatus is lifted from the skin, the ablated tissueportion is pulled out of the holes and the adhesion between theapparatus and the surrounding tissue is broken. In another embodiment,an array of probes is attached to the tissue removal apparatus and theprobes are applied to the skin region. The probes are aligned to beplaced in contact with the ablated tissue portions. The probe may beconstituted of a rigid cylinder in which the bottom surface is coveredwith an adhesive. Alternatively, the probe may be configured with a coldprobe that adheres to the skin due to low temperature. The probes may becombined with the surgical cutting mechanism or ablation apparatus.

In another embodiment, an ablated tissue portion may be removed byapplying a compressive force on the treatment area to squeeze the tissueout of the skin region. The compressive force can be applied by thefingers of the physician performing the ablation or by a tool, apparatusor device applying a controlled compressive force to the treatment area.

Vacuum

In one embodiment, a tissue removal apparatus with a vacuum may beapplied to an ablation apparatus or a skin region after formation of anablated tissue portion. For example, a tissue removal apparatus may beconfigured with an array of small access ports along the bottom of thechamber which may be applied to a skin region. The access ports thatcontact an ablated tissue portion may form a seal with the tissue. Uponseparation of the tissue removal apparatus from the skin region, theablated tissue portions are also removed.

In one embodiment, vacuum can ablate tissue by causing local boiling offor vaporization of tissue at ambient temperatures. In anotherembodiment, a vacuum is applied to micro-coring needle(s) or to circularblade(s) to facilitate detachment and removal of the tissue afterinsertion of the ablating member through the skin.

Thermal Removal

Thermal ablation can be used to remove an ablated tissue portion whenthe tissue portion is thermally isolated (e.g., ablated tissue or tissuefor removal is surrounded by a thermal insulating material) from thesurrounding tissue. In one embodiment, a micro-coring member (e.g.micro-coring needles, micro-coring paper drill, micro-coring hole saw,or micro-coring blade assembly) may be inserted in the skin to ablateand circumscribe the tissue without generation of thermal injury. Whilethe micro-coring member is still in the skin, an ablative laser may beused to vaporize the tissue contained in the micro-coring member. Themicro-coring apparatus material may be chosen to act as a thermalinsulator to prevent heating of the tissue outside of the micro-coringapparatus. In additional embodiments, any form of thermal ablation maybe used to remove a thermally isolated ablated tissue portion. Forexample and without limitation, any other method to convey heat in ashielded configuration may also work, such as use of a heated inner coreneedle, radiofrequency, ultrasound, and/or microscale application of ahot liquid or gas.

Resorption

Denatured tissue may also be resorbed in a skin region and replaced bynewly formed tissue. In an exemplary embodiment, an ablated tissueportion may be formed using a cryoneedle. The cryoneedle is removed anda compressive force is applied to the surrounding tissue, including theablated tissue portion. A dressing or closure may be applied to sustainthe compressive force. The ablated or damaged tissue from thecryosurgery may be resorbed thus allowing for the growth of new tissue.In another embodiment, an ablated tissue portion is desiccated (e.g.,water removed) using a strong vacuum. The desiccated tissue may then beresorbed in the skin region and be replaced by newly formed tissue. Inyet another embodiment, the tissue might not be compressed afterexposure to cold temperature, which can optionally lead to improvedtissue texture and appearance without significant tissue tightening

Liquefaction

Another apparatus and method for tissue removal includes liquefying thetissue with mechanical means. In one embodiment, a thin wire frame orgrid may be moved rapidly around an ablated tissue portion. The rapidand continuous cutting of the tissue eventually forms a liquid or gelfrom the ablated tissue portion. The tissue may be removed or drawn awayby vacuum. Another embodiment includes the use of a wire or fiber thatmay be attached to an axle and then rotated at or otherwise moved at ahigh speed to liquefy an ablated tissue portion. A pile driver, asdescribed herein, can cause liquefaction of tissue.

Positioning Apparatuses and Methods for Positioning Tissue

Holding tissue in place prior to, during or after ablation, and/ortissue removal may be more difficult when treating very lax tissue.Tissue positioning apparatuses of the invention facilitate ablation andtissue removal and also reduce errors in the skin treatment procedure. Askin positing apparatus may provide a compressive force and/or may beused to hold the skin in a desired xy dimension or lift the skin toelevate the dermis away from the underlying structures (e.g., sub-dermalmuscle layer, blood vessels, and nerve fibers) and prevent injuries tothese structures. Tissue positioning apparatuses may be combined with anablation apparatus and/or a tissue removal apparatus.

Tensioning

Surgeons put tissue under tension with their fingers before creating anincision with a scalpel. Prior to fractional ablation or tissue removal,the tissue may be placed under tension and/or provided as a flatsurface, which can be important for improving treatment outcome. In oneembodiment, two parallel rigid rods are applied on the skin. The rodmaterial is chosen to maximize its friction coefficient with the skin(e.g., rubber). The rods are first pushed toward the skin and then awayfrom each other in order to apply a tension on the skin surface. Theskin region between the rods essentially becomes planar. The formationof a flat surface allows for accurate positioning of an ablationapparatus above the skin region. When the ablation apparatus is an arrayof ablation apparatuses, the flat skin region allows for co-planarpositioning (e.g., x-y positioning) of the array. The skin region undertension facilitates the insertion of the penetrating components of anablation apparatus (e.g., a needle, drill, wire, or blade) into thetissue. The rods can rotate while maintaining the skin under tension toallow displacement of the ablation array. Another embodiment includesthe use of micro-hooks or micro-barbs to maintain tension in the skinregion. The micro-hooks are put under tension to flatten the skin in thetreatment area.

In yet another embodiment, instead of pulling the rods away from eachother, the rods can be pushed or rotated towards each other to pinch theskin and to exert a compressive force across the skin to elevate thedermis away from the underlying structures (e.g., sub-dermal musclelayer, blood vessels, and nerve fibers) (FIG. 22). A linear array ofmicro-coring needles may be placed in between the rods, which can berotated towards each other and allow movement of the apparatus acrossthe skin surface to be treated. The control of the rotation angle of therods allows control of the displacement of the treatment mechanism andthe treatment coverage. In this embodiment, using the rods to pinch theskin allows displacement of the treatment mechanism without releasingthe skin, thus, increasing treatment speed and allowing better controlof the treatment coverage.

In another embodiment, needles that provide a gripping force (“needlegrippers”) may be deployed in the dermis layer to lift the skin andelevate the dermis away from the underlying structures (e.g., sub-dermalmuscle layer, blood vessels, and nerve fibers). Once inserted in theskin (FIG. 23, arrow 1), opposite needles may be pulled away (FIG. 23,arrow 2) from each other to generate skin tension. The needles can thenbe pulled away from the skin surface to create a displacement of thedermis away from the underlying structures to prevent injury to muscle,blood vessels, and nerve fibers by the micro-coring needles. The levelof skin tension may be adjusted by pulling opposite needles away fromeach other in one direction to create a uni-directional skin tension.The needles may be retracted to release the skin. Needle grippers workon wet skin (i.e., when skin is covered with a liquid (e.g., blood)) andon partially treated skin (i.e. surface already punctured bymicro-coring needles).

In another embodiment, a flat surface with at least a hole is applied onthe skin, and the applied member is pushed towards the skin. The hole(s)in the surface allow access to the skin to the ablation member(s). Forexample and without limitation, one can envision a circular surface of3-4 cm in diameter with a hole in its center of 5 mm-1 cm. The circularmember is applied on the skin and pushed towards the skin as to put theskin exposed through the central hole under tension. The ablationmember(s) (e.g., one or more needles) are then positioned on top of thecentral hole and pushed through the skin.

In some embodiments, small non-circular holes are generated to promotewound healing. For example, pre-stretching the skin before ablation witha circular coring needle generates an elliptical hole in a non-stretchedskin, such as when the skin is once again relaxed. The long axis of theellipse is perpendicular to the pre-stretching direction. An ellipticalhole will generate skin tightening preferentially in the direction ofthe short axis of the ellipse.

In order to provide a tissue in a planar area positioned and undertension, a force may be provided to a skin region. A compression (orcompressive force, e.g., lateral compression), expansion (e.g., lateralexpansion), tension (e.g., as measured by tensile stress), stress (e.g.,as measured by compressive stress, shear stress, or tensile stress),load (e.g., load per millimeter width of at least 0.1 Newtons at astrain of at least 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09,0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or higher), or strain(e.g., as measured by deflection, deformation, strain at failure, orultimate strain (extension before rupture), e.g., greater than about 30%(e.g., greater than about 40%, 50%, 60%, 70%, 75%, 80%, 90%, 95%, 100%,110%, 115%, or 120%) or from about 30% to 130%) may be to be applied tothe skin region.

Vacuum

Vacuum may be used to pull lax skin under tension and pre-position askin region prior to fractional ablation. In one embodiment, a tube witha diameter large enough to surround an ablation apparatus or array ofablation apparatuses may be positioned on a skin region. A vacuum isapplied to the tube. As a result, the skin is pulled toward the tubeopening. The skin surface that faces the tube end is under tension andessentially flat. The skin region position is fixed relative to the tubeand to the ablation apparatus or array. Another benefit of thisembodiment is that the vacuum provides high gripping force and pulls theepidermal and dermal layer away from underlying structures (e.g. bloodvessels, nerve fibers, muscle). Without wishing to be limited bymechanism, use of vacuum could decrease the risk of collateral damageshould the ablation be too deep. In a further benefit of thisembodiment, the vacuum approach works to pull skin under tension evenwhen skin is wet (e.g., when skin is covered with a liquid (e.g.,blood)). Further, the vacuum may be used to pull the skin towards thefractional ablation tool (instead of lowering the tool towards theskin).

Airflow

A tissue positioning apparatus may alternatively include grippers thatuse airflow to adhere to the skin without physical contact. In oneembodiment, a gripper may use Bernoulli airflow (“a Bernoulli gripper”)to position the skin. A Bernoulli gripper relies on a pressurized airjet that generates a sub-atmospheric pressure of a radial airflow in asmall gap between the skin and the gripper (Dini et al., CIRPAnnals—Manufacturing Tech. 58:21-24, 2009), thus creating a vacuum-likeeffect without the use of a vacuum. One of the benefits of the Bernoulligripper is that it does not contact the skin. Without wishing to belimited by mechanism, use of Bernoulli airflow could limit the risk ofcontamination. In another embodiment, a gripper may use the Coandaejector (“a Coanda gripper”) to position the skin. The Coanda ejectorgenerates a gripping force by deflection of a pressurized airflow (Lienet al., CIRP Annals—Manufacturing Tech. 57:33-36, 2008). A Coandagripper may include an array of Coanda ejectors, which can position theskin by suction.

Cold Temperature

Cold objects adhere to the skin by freezing to the moisture from thetissue. A tissue positioning apparatus may include a cold surface thatmay be applied to the skin of the patient (e.g., a metal material at,for example, about −10 degrees C.). The tissue positioning apparatus mayalso include a series of channels through the cold surface to provideaccess to an ablation apparatus of a skin region. Tension may be appliedon the positioning device to lift the epidermal and dermal layer awayfrom underlying tissues prior to ablation. The cold temperature alsoreduces pain perception by the patient. To release the skin from thefreeze gripper, the skin can be mechanically detached from the gripper,e.g., by a “knife” mechanism introduced between the gripper and theskin. A benefit of the freeze gripper is that the freeze gripper worksto pull skin under tension even when skin is wet (e.g., when skin iscovered with a liquid (e.g., blood)) or when skin is partially treatedby mechanical fractional ablation.

Adhesive

In a further embodiment, tissue can be positioned using an apparatusthat includes an adhesive to hold a skin region. The adhesive may be ona surface of the device or on features attached to the device. In oneembodiment, a tissue positioning apparatus having an adhesive surfaceand a series of channels configured to accept an array of ablationapparatuses may be used to position a skin region by adhering to theskin region after being put under tension. The adhesive surface joinswith the skin region, thus maintaining the tension and providing a flatskin region. An array of ablation apparatuses may be moved through theaccess ports and used to ablate the tissue of the skin region.

Sensing

When the positioning and/or tensioning feature is integrated in thefractional ablation device, i.e. the device both allows positioning ofthe skin and tissue removal, it may be advantageous to have a mechanismthat ensures that the ablation apparatus is appropriately positionedbefore activation of the fractional ablation. One can envision a numberof sensing modalities including: a mechanical sensor (switch) that isactivated when the device presses on the skin, a temperature sensor thatdetects a temperature increase when the device is applied to the skinsurface, an optical sensor that detects skin proximity or microcontoursor ablations (e.g., to avoid overstrikes and/or to promote control ofspacing of ablations), or an inductive sensor that senses changes ininductive coupling due to the presence of electrically conductive skin.

The sensor can also be continuously monitored during the treatment toensure appropriate positioning of the device. The device may be stoppedwhen the sensor detects that the skin is not in contact with the device.

Exemplary Ablation Devices

An ablation apparatus, tissue removal apparatus, and tissue positionapparatus may be configured into a single device. Such a device providesseveral benefits, including ease of use, less time for the procedure,less time between ablation and closing of the ablated tissue portion,and more robust removal of ablated tissue portions. In one embodiment,an ablation apparatus is coupled into a device with a tissue removalapparatus using vacuum. The vacuum can be isolated from the deviceduring the ablation. After the ablation (e.g., drilling of a tissueportion to form a hole), the vacuum source may be joined to the deviceand the vacuum ports positioned over the drill holes to remove tissueand debris, thus completing the formation of an ablated tissue portion.In another embodiment, the tissue removal apparatus is configured toalso be a tissue positioning apparatus, both using vacuum. In thisembodiment, the ablation apparatus (e.g., a drill), tissue positioningapparatus, and tissue removal apparatus form a device which may bejoined to a vacuum apparatus configured to supply vacuum in twogeometries (e.g., a first vacuum geometry for positioning tissue and asecond vacuum, geometry for removing tissue). Prior to ablation, thevacuum source is joined to the tissue positioning configuration in thedevice and the skin region placed under tension. The device is broughtinto contact with the skin region and the tissue is held in a planarposition by the first vacuum geometry. The ablation component of thedevice is aligned and the drill enters the tissue to form holes. Afterdrilling, the second vacuum geometry is connected to the vacuum source,thus removing tissue and debris from the ablated tissue portions.Finally, the vacuum source is removed from the device releasing the skinregion from the positioning component of the device.

Healing of Skin Regions after Removal of Ablated Tissue Portions

A compressive wound dressing may be applied after ablation andsubsequent compression leads to skin tightening. The ablated tissueportion may be closed with a suture, staple, dressing, tunable dressing,glue, sealant, and other compression retaining devices. Such dressingsmay be applied in the proximity of the treatment zone or at a distantsite provided that it conveys the appropriate mechanical force on thetreatment site (e.g., by gluing the surrounding area into a compressedstate, which then confers compression to the treated area).

In one exemplary technique, a photosensitizer is applied to the tissue(e.g., Rose Bengal (RB) at concentration of less than 1.0% weight pervolume in a buffer, e.g., phosphate buffered saline to form a skintissue-RB complex), and then the tissue is irradiated withelectromagnetic energy to produce a seal (e.g., irradiated at awavelength of at least 488, at less than 2000 J/cm², and/or at less than1.5 W/cm², e.g., about 0.6 W/cm²). This exemplary technique is describedin U.S. Pat. No. 7,073,510, which is incorporated by reference in itsentirety. In another exemplary technique, a laser can be used for tissuewelding. In yet another exemplary technique, a photochemical agent isapplied to the tissue, and then the tissue is irradiated with visiblelight to produce a seal. In any of these embodiments, the techniqueincludes use of a bioerodible, unstable material that degradesspontaneously or in reaction to a treatment (e.g., such as anyresorbable or biodegradable material, including any described herein).

Materials

The methods, devices and apparatuses of the invention can include anyuseful materials.

Polymers and Plastics

An ablation apparatus, tissue removal apparatus, or tissue positioningapparatus may be formed from any useful polymer or plastic. Exemplarypolymers and plastics include, e.g., alginate, benzyl hyaluronate,carboxymethylcellulose, cellulose acetate, chitosan, collagen, dextran,epoxy, gelatin, hyaluronic acid, hydrocolloids, nylon (e.g., nylon 6 orPA6), pectin, poly (3-hydroxyl butyrate-co-poly (3-hydroxyl valerate),polyalkanes, polyalkene, polyalkynes, polyacrylate (PA),polyacrylonitrile (PAN), polybenzimidazole (PBI), polycarbonate (PC),polycaprolactone (PCL), polyester (PE), polyethylene glycol (PEG),polyethylene oxide (PEO), PEO/polycarbonate/polyurethane (PEO/PC/PU),poly(ethylene-co-vinyl acetate) (PEVA), PEVA/polylactic acid (PEVA/PLA),polyethylene, polypropylene, poly (ethylene terephthalate) (PET),PET/poly (ethylene naphthalate) (PET/PEN) polyglactin, polyglycolic acid(PGA), polyglycolic acid/polylactic acid (PGA/PLA), polyimide (PI),polylactic acid (PLA), poly-L-lactide (PLLA), PLLA/PC/polyvinylcarbazole(PLLA/PC/PVCB), poly (β-malic acid)-copolymers (PMLA), polymethacrylate(PMA), poly (methyl methacrylate) (PMMA), polystyrene (PS), polyurethane(PU), poly (vinyl alcohol) (PVA), polyvinylcarbazole (PVCB), polyvinylchloride (PVC), polyvinylidenedifluoride (PVDF), polyvinylpyrrolidone(PVP), silicone, rayon, polytetrafluoroethylene (PTFE), polyether etherketone (PEEK), or combinations thereof. The polymer or plastic of theinvention may be composite materials in which additives to the plastic,such as ceramics or particles, alter the mechanical properties.

Metals and Metal Alloys

An ablation apparatus, tissue removal apparatus, or tissue positioningapparatus may be formed from any useful metal or metal alloy. Exemplarymetals and alloys include stainless steel; titanium; a nickel-titanium(NiTi) alloy; a nickel-titanium-niobium (NiTiNb) alloy; anickel-iron-gallium (NiFeGa) alloy; a nickel-manganese-gallium (NiMnGa)alloy; a copper-aluminum-nickel (CuAlNi) allow; a copper-zinc (CuZn)alloy; a copper-tin (CuSn) alloy; a copper-zinc-aluminum (CuZnAl) alloy;a copper-zinc-silicon (CuZnSi) alloy; a copper-zinc-tin (CuZnSn) alloy;a copper-manganese alloy; a gold-cadmium (AuCd) alloy; a silver-cadmium(AgCd) alloy; an iron-platinum (FePt) alloy; an iron-manganese-silicon(FeMnSi) alloy; a cobalt-nickel-aluminum (CoNiAl) alloy; acobalt-nickel-gallium (CoNiGa) alloy; or a titanium-palladium (TiPd)alloy.

Adhesive Materials

A tissue removal apparatus and/or tissue positioning apparatus may usean adhesive. An adhesive may be located on an apparatus surface, the endof a probe, or another surface attached to a tissue removing or tissuepositioning apparatus.

The adhesive can be a pressure-sensitive adhesive (PSA). The propertiesof pressure sensitive adhesives are governed by three parameters, tack(initial adhesion), peel strength (adhesion), and shear strength(cohesion). Pressure-sensitive adhesives can be synthesized in severalways, including solvent-borne, water-borne, and hot-melt methods. Tackis the initial adhesion under slight pressure and short dwell time anddepends on the adhesive's ability to wet the contact surface. Peelstrength is the force required to remove the PSA from the contactsurface. The peel adhesion depends on many factors, including the tack,bonding history (e.g. force, dwell time), and adhesive composition.Shear strength is a measure of the adhesive's resistance to continuousstress. The shear strength is influenced by several parameters,including internal adhesion, cross-linking, and viscoelastic propertiesof the adhesive. Permanent adhesives are generally resistant todebonding and possess very high peel and shear strength.

Exemplary adhesives include a biocompatible matrix (e.g., thoseincluding at least one of collagen (e.g., a collagen sponge), lowmelting agarose (LMA), polylactic acid (PLA), and/or hyaluronic acid(e.g., hyaluranon); a photosensitizer (e.g., Rose Bengal,riboflavin-5-phosphate (R-5-P), methylene blue (MB),N-hydroxypyridine-2-(1H)-thione (N-HTP), a porphyrin, or a chlorin, aswell as precursors thereof); a photochemical agent (e.g., 1,8naphthalimide); a synthetic glue (e.g., a cyanoacrylate adhesive, apolyethylene glycol adhesive, or a gelatin-resorcinol-formaldehydeadhesive); a biologic sealant (e.g., a mixture of riboflavin-5-phosphateand fibrinogen, a fibrin-based sealant, an albumin-based sealant, or astarch-based sealant); or a hook or loop and eye system (e.g., as usedfor Velcro®). In particular embodiments, the adhesive is biodegradable.

Exemplary pressure-sensitive adhesives include natural rubber, syntheticrubber (e.g., styrene-butadiene and styrene-ethylene copolymers),polyvinyl ether, polyurethane, acrylic, silicones, and ethylene-vinylacetate copolymers. A copolymer's adhesive properties can be altered byvarying the composition (via monomer components) changing the glasstransition temperature (Tg) or degree of cross-linking. In general, acopolymer with a lower Tg is less rigid and a copolymer with a higher Tgis more rigid. The tack of PSAs can be altered by the addition ofcomponents to alter the viscosity or mechanical properties. Exemplarypressure sensitive adhesives are described in Czech et al.,“Pressure-Sensitive Adhesives for Medical Applications,” in Wide Spectraof Quality Control, Dr. Isin Akyar (Ed., published by InTech), Chapter17 (2011), which is hereby incorporated by reference in its entirety.

Therapeutic Agents

The ablation apparatuses and methods of the invention can include one ormore useful therapeutic agents. Exemplary agents include one or moregrowth factors (e.g., vascular endothelial growth factor (VEGF),platelet-derived growth factor (PDGF), transforming growth factor beta(TGF-β), fibroblast growth factor (FGF), epidermal growth factor (EGF),and keratinocyte growth factor); one or more stem cells (e.g., adiposetissue-derived stem cells and/or bone marrow-derived mesenchymal stemcells); one or more skin whitening agents (e.g., hydroquinone); one ormore vitamin A derivatives (e.g., tretinoin), one or more analgesics(e.g., paracetamol/acetaminophen, aspirin, a non-steroidalantiinflammatory drug, as described herein, a cyclooxygenase-2-specificinhibitor, as described herein, dextropropoxyphene, co-codamol, anopioid (e.g., morphine, codeine, oxycodone, hydrocodone,dihydromorphine, pethidine, buprenorphine, tramadol, or methadone),fentanyl, procaine, lidocaine, tetracaine, dibucaine, benzocaine,p-butylaminobenzoic acid 2-(diethylamino) ethyl ester HCl, mepivacaine,piperocaine, dyclonine, or venlafaxine); one or more antibiotics (e.g.,cephalosporin, bactitracin, polymyxin B sulfate, neomycin, bismuthtribromophenate, or polysporin); one or more antifungals (e.g.,nystatin); one or more antiinflammatory agents (e.g., a non-steroidalantiinflammatory drug (NSAID, e.g., ibuprofen, ketoprofen, flurbiprofen,piroxicam, indomethacin, diclofenac, sulindac, naproxen, aspirin,ketorolac, or tacrolimus), a cyclooxygenase-2-specific inhibitor (COX-2inhibitor, e.g., rofecoxib (Vioxx®), etoricoxib, and celecoxib(Celebrex®)), a glucocorticoid agent, a specific cytokine directed at Tlymphocyte function), a steroid (e.g., a corticosteroid, such as aglucocorticoid (e.g., aldosterone, beclometasone, betamethasone,cortisone, deoxycorticosterone acetate, dexamethasone, fludrocortisoneacetate, hydrocortisone, methylprednisolone, prednisone, prednisolone,or triamcinolone) or a mineralocorticoid agent (e.g., aldosterone,corticosterone, or deoxycorticosterone)), or an immune selectiveantiinflammatory derivative (e.g., phenylalanine-glutamine-glycine (FEG)and its D-isomeric form (feG))); one or more antimicrobials (e.g.,chlorhexidine gluconate, iodine (e.g., tincture of iodine,povidone-iodine, or Lugol's iodine), or silver, such as silver nitrate(e.g., as a 0.5% solution), silver sulfadiazine (e.g., as a cream), orAg⁺ in one or more useful carriers (e.g., an alginate, such as Acticoat®including nanocrystalline silver coating in high density polyethylene,available from Smith & Nephew, London, U.K., or Silvercel® including amixture of alginate, carboxymethylcellulose, and silver coated nylonfibers, available from Systagenix, Gatwick, U.K.; a foam (e.g.,Contreet® Foam including a soft hydrophilic polyurethane foam andsilver, available from Coloplast NS, Humlebæk, Denmark); a hydrocolloid(e.g., Aquacel® Ag including ionic silver and a hydrocolloid, availablefrom Conva Tec Inc., Skillman, N.J.); or a hydrogel (e.g., Silvasorb®including ionic silver, available from Medline Industries Inc.,Mansfield, Mass.)); one or more antiseptics (e.g., an alcohol, such asethanol (e.g., 60-90%), 1-propanol (e.g., 60-70%), as well as mixturesof 2-propanol/isopropanol; boric acid; calcium hypochlorite; hydrogenperoxide; manuka honey and/or methylglyoxal; a phenol (carbolic acid)compound, e.g., sodium 3,5-dibromo-4-hydroxybenzene sulfonate,trichlorophenylmethyl iodosalicyl, or triclosan; a polyhexanidecompound, e.g., polyhexamethylene biguanide (PHMB); a quaternaryammonium compound, such as benzalkonium chloride (BAC), benzethoniumchloride (BZT), cetyl trimethylammonium bromide (CTMB), cetylpyridiniumchloride (CPC), chlorhexidine (e.g., chlorhexidine gluconate), oroctenidine (e.g., octenidine dihydrochloride); sodium bicarbonate;sodium chloride; sodium hypochlorite (e.g., optionally in combinationwith boric acid in Dakin's solution); or a triarylmethane dye (e.g.,Brilliant Green)); one or more antiproliferative agents (e.g.,sirolimus, tacrolimus, zotarolimus, biolimus, or paclitaxel); one ormore emollients; one or more hemostatic agents (e.g., collagen, such asmicrofibrillar collagen, chitosan, calcium-loaded zeolite, cellulose,anhydrous aluminum sulfate, silver nitrate, potassium alum, titaniumoxide, fibrinogen, epinephrine, calcium alginate, poly-N-acetylglucosamine, thrombin, coagulation factor(s) (e.g., II, V, VII, VIII,IX, X, XI, XIII, or Von Willebrand factor, as well as activated formsthereof), a procoagulant (e.g., propyl gallate), an anti-fibrinolyticagent (e.g., epsilon aminocaproic acid or tranexamic acid), and thelike); one or more procoagulative agents (e.g., any hemostatic agentdescribed herein, desmopressin, coagulation factor(s) (e.g., II, V, VII,VIII, IX, X, XI, XIII, or Von Willebrand factor, as well as activatedforms thereof), procoagulants (e.g., propyl gallate), antifibrinolytics(e.g., epsilon aminocaproic acid), and the like); one or moreanticoagulative agents (e.g., heparin or derivatives thereof, such aslow molecular weight heparin, fondaparinux, or idraparinux; ananti-platelet agent, such as aspirin, dipyridamole, ticlopidine,clopidogrel, or prasugrel; a factor Xa inhibitor, such as a directfactor Xa inhibitor, e.g., apixaban or rivaroxaban; a thrombininhibitor, such as a direct thrombin inhibitor, e.g., argatroban,bivalirudin, dabigatran, hirudin, lepirudin, or ximelagatran; or acoumarin derivative or vitamin K antagonist, such as warfarin(coumadin), acenocoumarol, atromentin, phenindione, or phenprocoumon);one or more immune modulators, including corticosteroids andnon-steroidal immune modulators (e.g., NSAIDS, such as any describedherein); one or more proteins; or one or more vitamins (e.g., vitamin A,C, and/or E).

For the skin tightening methods described herein, the use ofanticoagulative and/or procoagulative agents may be of particularrelevance. For instance, by controlling the extent of bleeding and/orclotting in the ablations, the skin tightening effect can be moreeffectively controlled. Thus, in some embodiments, the methods anddevices herein include one or more anticoagulative agents, one or moreprocoagulative agents, one or more hemostatic agents, or combinationsthereof. In particular embodiments, the therapeutic agent controls theextent of bleeding and/or clotting in the treated skin region, includingthe use one or more anticoagulative agents (e.g., to inhibit clotformation prior to skin healing or slit/hole closure) and/or one or morehemostatic or procoagulative agents.

Kits, Optionally Including One or More Ablation Apparatuses, TissueRemoval Apparatuses, and/or Tissue Positioning Apparatuses

Also described herein are kits for skin tightening or for treatingdiseases, disorders, and conditions that would benefit from skinrestoration or tightening. Accordingly, the present invention includeskits having one or more ablation apparatuses, tissue removalapparatuses, and/or tissue positioning apparatuses, as well as kitshaving a combination of two or more apparatuses, where at least onedevice is an ablation apparatus as described herein. In addition, kitsof the invention may include one or more devices incorporating one ormore ablation apparatuses, tissue removal apparatuses, and/or tissuepositioning apparatuses in combination or individually.

The kit can include any other useful components. Exemplary componentsinclude instructions on how to use the device(s), an air blower, a heatgun, a heating pad, one or more therapeutic agents (e.g., any describedherein, such as an anticoagulative and/or procoagulative agent, andoptionally in combination with a useful dispenser for applying thetherapeutic agent, such as a brush, spray, film, ointment, cream,lotion, or gel), one or more wound cleansers (e.g., including anyantibiotic, antimicrobial, or antiseptic, such as those describedherein, in any useful form, such as a brush, spray, film, ointment,cream, lotion, or gel), one or more compression dressings (e.g., asdescribed herein), one or more closures (e.g., bandage, hemostats,sutures, or adhesives), one or more debriding agents, one or moreadhesives (e.g., any described herein), one or more cosmetics (e.g., asdescribed herein), and/or other suitable or useful materials.

Methods for Treating Skin Regions

The present invention relates to apparatuses, methods, and devices thatcan be applied to treat one or more skin regions. In particularembodiments, these regions are treated with one or more procedures toimprove skin appearance. Accordingly, the devices, ablation apparatuses,tissue removing and tissue positioning apparatuses, and methods hereincan be useful for skin rejuvenation (e.g., removal of pigment, veins(e.g., spider veins or reticular veins), and/or vessels in the skin) orfor treating acne, allodynia, blemishes, ectopic dermatitis,hyperpigmentation, hyperplasia (e.g., lentigo or keratosis), loss oftranslucency, loss of elasticity, melasma (e.g., epidermal, dermal, ormixed subtypes), photodamage, rashes (e.g., erythematous, macular,papular, and/or bullous conditions), psoriasis, rhytides (or wrinkles,e.g., crow's feet, age-related rhytides, sun-related rhytides, orheredity-related rhytides), sallow color, scar contracture (e.g.,relaxation of scar tissue), scarring (e.g., due to acne, surgery, orother trauma), skin aging, skin contraction (e.g., excessive tension inthe skin), skin irritation/sensitivity, skin laxity (e.g., loose orsagging skin or other skin irregularities), striae (or stretch marks),tattoo removal, vascular lesions (e.g., angioma, erythema, hemangioma,papule, port wine stain, rosacea, reticular vein, or telangiectasia), orany other unwanted skin irregularities.

Such treatments can be include any parts of the body, including the face(e.g., eyelid, cheeks, chin, forehead, lips, or nose), neck, chest(e.g., as in a breast lift), arms, hands, legs, abdomen, and/or back.Accordingly, the apparatuses of the invention can be arranged orconfigured to be amenable to the size or geometry of different bodyregions. Such arrangements and configurations can include any usefulshape (e.g., linear, curved, or stellate), size, and/or depth.

In general, the treatment methods include forming a series of smallwounds formed by the ablation of tissue (e.g., removal of ablated tissueportions). These small wounds (e.g., microwounds) reduce tissue volumeor improve tissue quality upon healing. For example, a series of ablatedtissue portions (e.g., ablation of about 5-40% (e.g., 10-40%) of thetotal skin area) in high laxity skin region can be compressed to closethe wounds and promote the growth of new skin (i.e. improved tissue).Healing of the tissue under compression allows for the existing tissueto span the gap introduced by the ablated tissue portion, thereforereducing the skin volume and skin areal dimension (i.e. tightening theskin).

In one embodiment, ablated tissue portions are formed using a hollowblade or micro-coring needle. Prior to ablation, the skin region can beput under tension to create a flat skin region using a tissuepositioning device. The tissue positioning device maintains the tensionforce on the skin region during the ablation. An ablation apparatus ispositioned over the skin region. The hollow blades are inserted into theskin region to circumscribe tissue with a dimension less than 1 mm. Thehollow blade is removed leaving behind the ablated tissue portion. Theablated tissue portion is removed from the skin region using a tissueremoval apparatus, such as an adhesive device or vacuum device. Once theablated tissue portion is formed, the resulting hole can be compressedand sealed using a dressing, closure, glue, or suture.

In one exemplary procedure, a plurality of tissue portions are ablatedfrom a skin region in a subject (e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10,15, 20, 25, 30, 35, 40, 45, 50, 75, 100, or more tissue portions, suchas between about 2 and 100 tissue portions (e.g., between 2 and 10, 2and 15, 2 and 20, 2 and 25, 2 and 30, 2 and 35, 2 and 40, 2 and 45, 2and 50, 2 and 75, 5 and 10, 5 and 15, 5 and 20, 5 and 25, 5 and 30, 5and 35, 5 and 40, 5 and 45, 5 and 50, 5 and 75, 5 and 100, 10 and 20, 10and 25, 10 and 30, 10 and 35, 10 and 40, 10 and 45, 10 and 50, 10 and75, 10 and 100, 15 and 20, 15 and 25, 15 and 30, 15 and 35, 15 and 40,15 and 45, 15 and 50, 15 and 75, 15 and 100, 20 and 25, 20 and 30, 20and 35, 20 and 40, 20 and 45, 20 and 50, 20 and 75, 20 and 100, 25 and30, 25 and 35, 25 and 40, 25 and 45, 25 and 50, 25 and 75, 25 and 100,30 and 35, 30 and 40, 30 and 45, 30 and 50, 30 and 75, 30 and 100, 35and 40, 35 and 45, 35 and 50, 35 and 75, 35 and 100, 40 and 45, 40 and50, 40 and 75, 40 and 100, 50 and 75, or 50 and 100)). In anotherexemplary procedure, hundreds to thousands of hole per squarecentimeters are ablated from a skin region in a subject (e.g., manythousands of holes in total to treat a large area (e.g., the arm)), suchas from about 10 to about 10000 ablated tissue portions per cm² area ofthe skin region, as described herein and in Table 1.

Such tissue portions can be included in any useful geometric,non-geometric, or random array (e.g., such as those described herein foran array of tubes and/or blades). Such tissue portions can have anyuseful dimension that promotes wound or skin healing. Non-limitingdimensions of a tissue portion includes at least one dimension that isless than about 2.0 mm (e.g., less than or equal to about 1.5 mm, 1 mm,0.75 mm, 0.5 mm, 0.3 mm, 0.2 mm, 0.1 mm, 0.075 mm, 0.05 mm, or 0.025 mm)or between about 0.025 mm and 2.0 mm (e.g., between about 0.025 mm and1.5 mm, 0.025 mm and 1.0 mm, 0.025 mm and 0.75 mm, 0.025 mm and 0.5 mm,0.025 mm and 0.3 mm, 0.025 mm and 0.2 mm, 0.025 mm and 0.1 mm, 0.025 mmand 0.075 mm, 0.025 mm and 0.05 mm, 0.05 mm and 2.0 mm, 0.05 mm and 1.5mm, 0.05 mm and 1.0 mm, 0.05 mm and 0.75 mm, 0.05 mm and 0.5 mm, 0.05 mmand 0.3 mm, 0.05 mm and 0.2 mm, 0.05 mm and 0.1 mm, 0.05 mm and 0.075mm, 0.075 mm and 2.0 mm, 0.075 mm and 1.5 mm, 0.075 mm and 1.0 mm, 0.075mm and 0.75 mm, 0.075 mm and 0.5 mm, 0.075 mm and 0.3 mm, 0.075 mm and0.2 mm, 0.075 mm and 0.1 mm, 0.1 mm and 2.0 mm, 0.1 mm and 1.5 mm, 0.1mm and 1.0 mm, 0.1 mm and 0.75 mm, 0.1 mm and 0.5 mm, 0.1 mm and 0.3 mm,0.1 mm and 0.2 mm, 0.2 mm and 2.0 mm, 0.2 mm and 1.5 mm, 0.2 mm and 1.0mm, 0.2 mm and 0.75 mm, 0.2 mm and 0.5 mm, 0.2 mm and 0.3 mm, 0.3 mm and2.0 mm, 0.3 mm and 1.5 mm, 0.3 mm and 1.0 mm, 0.3 mm and 0.75 mm, 0.3 mmand 0.5 mm, 0.5 mm and 2.0 mm, 0.5 mm and 1.5 mm, 0.5 mm and 1.0 mm, 0.5mm and 0.75 mm, 0.75 mm and 2.0 mm, 0.75 mm and 1.5 mm, or 0.75 mm and1.0 mm).

In some embodiments, the ablated tissue portions forms a hole in theskin region, where the diameter or width of the hole is less than about1.0 mm and results in a tissue portion having a diameter or width thatis less than about 1.0 mm. In further embodiments, the tissue portionhas a diameter or width that is less than about 1.0 mm and a length ofmore than about 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm. 2.5 mm, 3.0mm, or 3.5 mm). In particular embodiments, relatively small dimensionsof the tissue portions can promote healing while minimizing theformation of scars. In some embodiments, the ablated tissue portionshave width to depth ratios including ratios between 1:0.3 to 1:75 (e.g.,1:0.3 to 1:50, 1:0.3 to 1:25, 1:0.3 to 1:5, 1:0.3 to 1:1, 1:1 to 1:75,1:1 to 1:50, 1:1 to 1:25, 1:1 to 1:5). In other embodiments, the ablatedtissue portions have width to depth ratios including ratios between1:0.3 to 1:1 (e.g., 1:0.3 to 1:1, 1:0.35 to 1:1, 1:0.4 to 1:1, 1:0.45 to1:1, 1:0.5 to 1:1, 1:1 to 0.55 to 1:1, 1:0.6 to 1:1, 1:0.65 to 1:1,1:0.7 to 1:1, 1:0.75 to 1:1, 1:0.8 to 1:1, 1:0.85 to 1:1, 1:0.9 to 1:1,1:0.95 to 1:1, 1:0.3 to 1:0.95, 1:0.35 to 1:0.95, 1:0.4 to 1:0.95,1:0.45 to 1:0.95, 1:0.5 to 1:0.95, 1:0.95 to 0.55 to 1:0.95, 1:0.6 to1:0.95, 1:0.65 to 1:0.95, 1:0.7 to 1:0.95, 1:0.75 to 1:0.95, 1:0.8 to1:0.95, 1:0.85 to 1:0.95, 1:0.9 to 1:0.95, 1:0.3 to 1:0.9, 1:0.35 to1:0.9, 1:0.4 to 1:0.9, 1:0.45 to 1:0.9, 1:0.5 to 1:0.9, 1:0.9 to 0.55 to1:0.9, 1:0.6 to 1:0.9, 1:0.65 to 1:0.9, 1:0.7 to 1:0.9, 1:0.75 to 1:0.9,1:0.8 to 1:0.9, 1:0.85 to 1:0.9, 1:0.3 to 1:0.85, 1:0.35 to 1:0.85,1:0.4 to 1:0.85, 1:0.45 to 1:0.85, 1:0.5 to 1:0.85, 1:0.85 to 0.55 to1:0.85, 1:0.6 to 1:0.85, 1:0.65 to 1:0.85, 1:0.7 to 1:0.85, 1:0.75 to1:0.85, 1:0.8 to 1:0.85, 1:0.3 to 1:0.8, 1:0.35 to 1:0.8, 1:0.4 to1:0.8, 1:0.45 to 1:0.8, 1:0.5 to 1:0.8, 1:0.8 to 0.55 to 1:0.8, 1:0.6 to1:0.8, 1:0.65 to 1:0.8, 1:0.7 to 1:0.8, 1:0.75 to 1:0.8, 1:0.3 to1:0.75, 1:0.35 to 1:0.75, 1:0.4 to 1:0.75, 1:0.45 to 1:0.75, 1:0.5 to1:0.75, 1:0.75 to 0.55 to 1:0.75, 1:0.6 to 1:0.75, 1:0.65 to 1:0.75,1:0.7 to 1:0.75, 1:0.3 to 1:0.65, 1:0.35 to 1:0.65, 1:0.4 to 1:0.65,1:0.45 to 1:0.65, 1:0.5 to 1:0.65, 1:0.65 to 0.55 to 1:0.65, 1:0.6 to1:0.65, 1:0.3 to 1:0.65, 1:0.35 to 1:0.65, 1:0.4 to 1:0.65, 1:0.45 to1:0.65, 1:0.5 to 1:0.65, 1:0.65 to 0.55 to 1:0.65, 1:0.6 to 1:0.65,1:0.3 to 1:0.6, 1:0.35 to 1:0.6, 1:0.4 to 1:0.6, 1:0.45 to 1:0.6, 1:0.5to 1:0.6, 1:0.6 to 0.55 to 1:0.6, 1:0.3 to 1:0.55, 1:0.35 to 1:0.55,1:0.4 to 1:0.55, 1:0.45 to 1:0.55, 1:0.5 to 1:0.55, 1:0.3 to 1:0.5,1:0.35 to 1:0.5, 1:0.4 to 1:0.5, 1:0.45 to 1:0.5, 1:0.5 to 1:0.5, 1:0.3to 1:0.45, 1:0.35 to 1:0.45, 1:0.4 to 1:0.45, 1:0.3 to 1:0.4, 1:0.35 to1:0.4, or 1:0.3 to 1:0.35) and 1:25 to 1:75 (e.g., 1:25 to 1:75, 1:30 to1:75, 1:35 to 1:75, 1:40 to 1:75, 1:45 to 1:75, 1:50 to 1:75, 1:55 to1:75, 1:60 to 1:75, 1:65 to 1:75, 1:70 to 1:75, 1:25 to 1:70, 1:30 to1:70, 1:35 to 1:70, 1:40 to 1:70, 1:45 to 1:70, 1:50 to 1:70, 1:55 to1:70, 1:60 to 1:70, 1:65 to 1:70, 1:25 to 1:65, 1:30 to 1:65, 1:35 to1:65, 1:40 to 1:65, 1:45 to 1:65, 1:50 to 1:65, 1:55 to 1:65, 1:60 to1:65, 1:25 to 1:60, 1:30 to 1:60, 1:35 to 1:60, 1:40 to 1:60, 1:45 to1:60, 1:50 to 1:60, 1:55 to 1:60, 1:25 to 1:55, 1:30 to 1:55, 1:35 to1:55, 1:40 to 1:55, 1:45 to 1:55, 1:50 to 1:55, 1:25 to 1:50, 1:30 to1:50, 1:35 to 1:50, 1:40 to 1:50, 1:45 to 1:50, 1:25 to 1:45, 1:30 to1:45, 1:35 to 1:45, 1:40 to 1:45, 1:25 to 1:40, 1:30 to 1:40, 1:35 to1:40, 1:25 to 1:35, 1:30 to 1:35, or 1:25 to 1:30).

Exemplary ablated tissue portion widths include from about 0.1 mm toabout 0.8 mm (e.g., 0.1 mm to 0.8 mm, 0.1 mm to 0.6 mm, 0.1 mm to 0.4mm, 0.1 mm to 0.2 mm, 0.2 mm to 0.8 mm, 0.2 mm to 0.6 mm, 0.2 mm to 0.4mm, 0.2 mm to 0.3 mm, 0.3 mm to 0.8 mm, 0.3 mm to 0.6 mm, 0.3 mm to 0.4mm, 0.4 mm to 0.8 mm, 0.4 mm to 0.6 mm, 0.4 mm to 0.5 mm, 0.5 mm to 0.8mm, 0.5 mm to 0.6 mm, 0.6 mm to 0.8 mm, 0.6 mm to 0.7 mm, or 0.7 mm to0.8 mm). Exemplary ablated tissue portion widths includes 0.9 mm to 20mm (e.g., 0.9 mm to 20 mm, 0.9 mm to 17 mm, 0.9 mm to 14 mm, 0.9 mm to11 mm, 0.9 mm to 8 mm, 0.9 mm to 5 mm, 0.9 mm to 3 mm, 3 mm to 20 mm, 3mm to 17 mm, 3 mm to 14 mm, 3 mm to 11 mm, 3 mm to 8 mm, 3 mm to 5 mm, 5mm to 20 mm, 5 mm to 17 mm, 5 mm to 14 mm, 5 mm to 11 mm, 5 mm to 8 mm,8 mm to 20 mm, 8 mm to 17 mm, 8 mm to 14 mm, 8 mm to 11 mm, 11 mm to 20mm, 11 mm to 17 mm, 11 mm to 14 mm, 14 mm to 20 mm, 14 mm to 17 mm, or17 mm to 20 mm) and 0.01 mm to 0.25 mm (e.g., 0.01 mm to 0.25 mm, 0.02mm to 0.25 mm, 0.03 mm to 0.25 mm, 0.05 mm to 0.25 mm, 0.075 mm to 0.25mm, 0.1 mm to 0.25 mm, 0.15 mm to 0.25 mm, 0.2 mm to 0.25 mm, 0.01 mm to0.2 mm, 0.02 mm to 0.2 mm, 0.03 mm to 0.2 mm, 0.05 mm to 0.2 mm, 0.075mm to 0.2 mm, 0.1 mm to 0.2 mm, 0.15 mm to 0.2 mm, 0.01 mm to 0.15 mm,0.02 mm to 0.15 mm, 0.03 mm to 0.15 mm, 0.05 mm to 0.15 mm, 0.075 mm to0.15 mm, 0.1 mm to 0.15 mm, 0.01 mm to 0.1 mm, 0.02 mm to 0.1 mm, 0.03mm to 0.1 mm, 0.05 mm to 0.1 mm, 0.075 mm to 0.1 mm, 0.01 mm to 0.075mm, 0.02 mm to 0.075 mm, 0.03 mm to 0.075 mm, 0.05 mm to 0.075 mm, 0.01mm to 0.05 mm, 0.02 mm to 0.05 mm, 0.03 mm to 0.05 mm, 0.01 mm to 0.03mm, 0.02 mm to 0.03 mm, 0.03 mm to 0.03 mm, 0.01 mm to 0.03 mm, 0.02 mmto 0.03 mm, or 0.01 mm to 0.02 mm).

In other embodiments, the ablated tissue portions forms a slit in theskin region, where the length or width of the slit is less than about1.0 mm and results in a tissue portion having a length or width that isless than about 1.0 mm. In further embodiments, the tissue portion has alength or width that is less than about 1.0 mm and a length of more thanabout 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm. 2.5 mm, 3.0 mm, 3.5mm, 4.0 mm, 4.5 mm, 5.0 mm, 5.5 mm, or 6.0 mm). In particularembodiments, relatively small dimensions of the tissue portions canpromote healing while minimizing the formation of scars.

When viewed from the top of the skin (i.e., along the z-direction orwithin the xy-plane of the skin), the shape of the hole can be circularor non-circular (e.g., elliptical). Exemplary shapes of tissue portionsare provided in FIGS. 1A-1C and 3A-3C and its associated text of U.S.Pub. No. 2012/0041430, which are hereby incorporated by reference in itsentirety.

Any beneficial areal fraction of the skin region can be removed, such asan areal fraction of less than about 70% (e.g., less than about 65%,60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 10%, or 5%) or such asbetween about 5% and 80% (e.g., between about 5% and 10%, 5% and 10%, 5%and 20%, 5% and 25%, 5% and 30%, 5% and 35%, 5% and 40%, 5% and 45%, 5%and 50%, 5% and 55%, 5% and 60%, 5% and 65%, 5% and 70%, 5% and 75%, 10%and 10%, 10% and 20%, 10% and 25%, 10% and 30%, 10% and 35%, 10% and40%, 10% and 45%, 10% and 50%, 10% and 55%, 10% and 60%, 10% and 65%,10% and 70%, 10% and 75%, 10% and 80%, 15% and 20%, 15% and 25%, 15% and30%, 15% and 35%, 15% and 40%, 15% and 45%, 15% and 50%, 15% and 55%,15% and 60%, 15% and 65%, 15% and 70%, 15% and 75%, 15% and 80%, 20% and25%, 20% and 30%, 20% and 35%, 20% and 40%, 20% and 45%, 20% and 50%,20% and 55%, 20% and 60%, 20% and 65%, 20% and 70%, 20% and 75%, or 20%and 80%).

The skin region can be removed with various hole density (i.e., numberof holes per unit area) for different skin-penetrating component sizesand different areal fractions. As a non-limiting example, Table 1 belowprovides the calculated number of holes for a particular areal fraction(column labeled “Percentage removed”) of a treatment region (columnlabeled “Treatment area length” and “Treatment area width”) using aparticular needle gauge. In some embodiments, 21 to 24 gauge needles arepreferred. In particular, 22 gauge needles are preferred. In somepreferred embodiments, 5-20% of treatment region is removed, forexample, using 21-24 gauge needles (e.g., 22 gauge needles). The numberof holes can be attained by using a single needle and actuating theneedle across the treatment area. Alternatively, the number of holes canbe attained by using an array of needles and repeatedly actuating theacross the treatment area. For example, for 14 holes using a 19 gaugeneedle (first row, excluding header, in Table 1), a single needle can beactuated 14 times, or an array having about 5 needles can be actuatedthree times (to provide an average of 15 holes in the treatment area) inthe treatment area. As can be seen by the latter example, the number ofholes obtained from a calculation are only approximations to guide theuser. Taking another example, for 4,366 holes using a 33 gauge needle(last row in Table 1), a single needle can be actuated 4,366 times.Alternatively, an array having an x number of needles can be actuated4,366/x times. For instance, if the array has 10 needles, the array canbe actuated about 437 times to obtain the intended areal coverage. Inanother instance, if the array has 20 needles, the array can be actuatedabout 218 times to obtain the intended areal coverage. Further guidanceare provided herein, e.g., in Example 11 for providing calculations todetermine the surface of tissue removed by a single skin-penetratingcomponent and the time required to remove the total tissue surface.

TABLE 1 Hole Treatment Treatment Holes Needle diameter Surface/hole arealength area width Percentage Number per area gauge [μm] [mm²] [mm] [mm]removed of holes [1/cm²] 19 686 0.370 10 10  5% 14 13.53 19 686 0.370 1010 10% 27 27.06 19 686 0.370 10 10 40% 108 108.22 20 603 0.286 10 10  5%18 17.51 20 603 0.286 10 10 10% 35 35.02 20 603 0.286 10 10 40% 140140.07 21 514 0.207 10 10  5% 24 24.10 21 514 0.207 10 10 10% 48 48.1921 514 0.207 10 10 40% 193 192.77 22 413 0.134 10 10  5% 37 37.32 22 4130.134 10 10 10% 75 74.65 22 413 0.134 10 10 40% 299 298.59 24 311 0.07610 10  5% 66 65.82 24 311 0.076 10 10 10% 132 131.64 24 311 0.076 10 1040% 527 526.56 25 260 0.053 10 10  5% 94 94.17 25 260 0.053 10 10 10%188 188.35 25 260 0.053 10 10 40% 753 753.40 27 210 0.035 10 10  5% 144144.36 27 210 0.035 10 10 10% 289 288.72 25 210 0.035 10 10 40% 1,1551154.87 33 108 0.009 10 10  5% 546 545.80 33 108 0.009 10 10 10% 1,0921091.60 33 108 0.009 10 10 40% 4,366 4366.39

A plurality of tissue portions can be ablated from a treatment region.In particular embodiments, the apparatus or device, e.g., any describedherein, are configured to provide more than about 10 ablated tissueportions per cm² area of the skin region (e.g., more than about 15, 20,30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500,550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1250, 1500, 1750,2000, 2250, 2500, 2750, 3000, 3250, 3500, 3750, 4000, 4250, 4500, 4750,5000, 5250, 5500, 5750, 6000, 6250, 6500, 6750, 7000, 7250, 7500, 7750,8000, 8250, 8500, 8750, 9000, 9250, 9500, 9750, or 10000 ablated tissueportions per cm² area of the skin region). In other embodiments, theapparatus or device, e.g., any described herein, are configured toprovide from about 10 to about 10000 ablated tissue portions per cm²area of the skin region (e.g., from 15 to 500, 20 to 500, 30 to 500, 40to 500, 50 to 500, 60 to 500, 70 to 500, 80 to 500, 90 to 500, 100 to500, 150 to 500, 200 to 500, 250 to 500, 300 to 500, 350 to 500, 400 to500, 450 to 500, 15 to 1000, 20 to 1000, 30 to 1000, 40 to 1000, 50 to1000, 60 to 1000, 70 to 1000, 80 to 1000, 90 to 1000, 100 to 1000, 150to 1000, 200 to 1000, 250 to 1000, 300 to 1000, 350 to 1000, 400 to1000, 450 to 1000, 500 to 1000, 550 to 1000, 600 to 1000, 650 to 1000,700 to 1000, 750 to 1000, 800 to 1000, 850 to 1000, 900 to 1000, 950 to1000, 15 to 5000, 20 to 5000, 30 to 5000, 40 to 5000, 50 to 5000, 60 to5000, 70 to 5000, 80 to 5000, 90 to 5000, 100 to 5000, 150 to 5000, 200to 5000, 250 to 5000, 300 to 5000, 350 to 5000, 400 to 5000, 450 to5000, 500 to 5000, 550 to 5000, 600 to 5000, 650 to 5000, 700 to 5000,750 to 5000, 800 to 5000, 850 to 5000, 900 to 5000, 950 to 5000, 1000 to5000, 1250 to 5000, 1500 to 5000, 1750 to 5000, 2000 to 5000, 2250 to5000, 2500 to 5000, 2750 to 5000, 3000 to 5000, 3250 to 5000, 3500 to5000, 3750 to 5000, 4000 to 5000, 4250 to 5000, 4500 to 5000, 4750 to5000, 15 to 7500, 20 to 7500, 30 to 7500, 40 to 7500, 50 to 7500, 60 to7500, 70 to 7500, 80 to 7500, 90 to 7500, 100 to 7500, 150 to 7500, 200to 7500, 250 to 7500, 300 to 7500, 350 to 7500, 400 to 7500, 450 to7500, 500 to 7500, 550 to 7500, 600 to 7500, 650 to 7500, 700 to 7500,750 to 7500, 800 to 7500, 850 to 7500, 900 to 7500, 950 to 7500, 1000 to7500, 1250 to 7500, 1500 to 7500, 1750 to 7500, 2000 to 7500, 2250 to7500, 2500 to 7500, 2750 to 7500, 3000 to 7500, 3250 to 7500, 3500 to7500, 3750 to 7500, 4000 to 7500, 4250 to 7500, 4500 to 7500, 4750 to7500, 5000 to 7500, 5250 to 7500, 5500 to 7500, 5750 to 7500, 6000 to7500, 6250 to 7500, 6500 to 7500, 6750 to 7500, 7000 to 7500, 7250 to7500, 15 to 10000, 20 to 10000, 30 to 10000, 40 to 10000, 50 to 10000,60 to 10000, 70 to 10000, 80 to 10000, 90 to 10000, 100 to 10000, 150 to10000, 200 to 10000, 250 to 10000, 300 to 10000, 350 to 10000, 400 to10000, 450 to 10000, 500 to 10000, 550 to 10000, 600 to 10000, 650 to10000, 700 to 10000, 750 to 10000, 800 to 10000, 850 to 10000, 900 to10000, 950 to 10000, 1000 to 10000, 1250 to 10000, 1500 to 10000, 1750to 10000, 2000 to 10000, 2250 to 10000, 2500 to 10000, 2750 to 10000,3000 to 10000, 3250 to 10000, 3500 to 10000, 3750 to 10000, 4000 to10000, 4250 to 10000, 4500 to 10000, 4750 to 10000, 5000 to 10000, 5250to 10000, 5500 to 10000, 5750 to 10000, 6000 to 10000, 6250 to 10000,6500 to 10000, 6750 to 10000, 7000 to 10000, 7250 to 10000, 7500 to10000, 7750 to 10000, 8000 to 10000, 8250 to 10000, 8500 to 10000, 8750to 10000, 9000 to 10000, 9250 to 10000, 9500 to 10000, and 9750 to 10000ablated tissue portions per cm² area of the skin region).

Furthermore, the plurality of tissue portions can be ablated in anybeneficial pattern within the skin region. Exemplary patterns within theskin region include tile patterns or fractal-like shapes, where thearray of hollow tubes can be arranged, e.g., in a base, to effectuatesuch a pattern. For example, a higher density and/or smaller spacing oftissue portions (e.g., slits and/or holes) can be ablated in the skin incenter of the pattern or in thicker portions of the skin. In anotherexample, the pattern within the skin can be random, staggered rows,parallel rows, a circular pattern, a spiral pattern, a square orrectangular pattern, a triangular pattern, a hexagonal pattern, a radialdistribution, or a combination of one or more such patterns of theablated tissue portions. The pattern can arise from modifications to theaverage length, depth, or width of an ablated tissue portion, as well asthe density, orientation, and spacing between such ablations (e.g., byusing an ablation apparatus or an array of ablation apparatuses havingone or more blades or tubes with differing lengths, widths, orgeometries that are arranged in a particular density or spacingpattern). Such patterns can be optimized to promote unidirectional,non-directional, or multidirectional contraction or expansion of skin(e.g., in the x-direction, y-direction, x-direction, x-y plane, y-zplane, x-z plane, and/or xyz-plane), such as by modifying the averagelength, depth, width, density, orientation, and/or spacing betweenablations.

Any useful portion of the skin or underlying structures (e.g. SMAS) canbe ablated. Such tissue portions can include epidermal tissue, dermaltissue, and/or cells or tissue proximal to the dermal/fatty layerboundary (e.g., stem cells). In particular embodiments, ablated tissueportions forms a hole in the skin region, where the depth of the hole ismore than about 1.0 mm and results in a tissue portion having a lengththat is more than about 1.0 mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm. 2.5mm, 3.0 mm, 3.5 mm, 4.0 mm. 4.5 mm, 5.0 mm, 5.5 mm, or 6.0 mm). Inparticular embodiments, the ablated tissue portions forms a slit in theskin region, where the depth of the slit is more than about 1.0 mm andresults in a tissue portion having a length that is more than about 1.0mm (e.g., about 1.0 mm, 1.5 mm, 2.0 mm. 2.5 mm, 3.0 mm, 3.5 mm, 4.0 mm.4.5 mm, 5.0 mm, 5.5 mm, or 6.0 mm). In some embodiments, the tissueportion has a length that corresponds to a typical total depth of theskin layer (e.g., epidermal and dermal layers). Based on the part of thebody, the total depth of the epidermal and dermal layers can vary. Insome embodiments, the depth of the epidermal layer is between about 0.8mm to 1.4 mm, and/or the depth of the dermal layer is between about 0.3mm to 6.0 mm. In other embodiments, the total depth of the skin layer(e.g., epidermal and dermal layers) is between about 0.9 mm and 6.0 mm,thereby resulting in a tissue portion having a length between about 0.9mm and 6.0 mm (e.g., between about 0.9 mm and 1.5 mm, 0.9 mm and 2.0 mm,0.9 mm and 2.5 mm, 0.9 mm and 3.0 mm, 0.9 mm and 3.5 mm, 0.9 mm and 4.0mm, 0.9 mm and 4.5 mm, 0.9 mm and 5.0 mm, 0.9 mm and 5.5 mm, 0.9 mm and6.0 mm, 1.5 mm and 2.0 mm, 1.5 mm and 2.5 mm, 1.5 mm and 3.0 mm, 1.5 mmand 3.5 mm, 1.5 mm and 4.0 mm, 1.5 mm and 4.5 mm, 1.5 mm and 5.0 mm, 1.5mm and 5.5 mm, 1.5 mm and 6.0 mm, 2.0 mm and 2.5 mm, 2.0 mm and 3.0 mm,2.0 mm and 3.5 mm, 2.0 mm and 4.0 mm, 2.0 mm and 4.5 mm, 2.0 mm and 5.0mm, 2.0 mm and 5.5 mm, 2.0 and 6.0 mm, 2.5 mm and 3.0 mm, 2.5 mm and 3.5mm, 2.5 mm and 4.0 mm, 2.5 mm and 4.5 mm, 2.5 mm and 5.0 mm, 2.5 mm and5.5 mm, 2.5 mm and 6.0 mm, 3.0 mm and 3.5 mm, 3.0 mm and 4.0 mm, 3.0 mmand 4.5 mm, 3.0 mm and 5.0 mm, 3.0 mm and 5.5 mm, 3.0 and 6.0 mm, 3.5 mmand 4.0 mm, 3.5 mm and 4.5 mm, 3.5 mm and 5.0 mm, 3.5 mm and 5.5 mm, 3.5and 6.0 mm, 4.0 mm and 4.5 mm, 4.0 mm and 5.0 mm, 4.0 mm and 5.5 mm, 4.0and 6.0 mm, 4.5 mm and 5.0 mm, 4.5 mm and 5.5 mm, 4.5 and 6.0 mm, 5.0 mmand 5.5 mm, 5.0 mm and 6.0 mm, or 5.5 mm and 6.0 mm). In yet otherembodiments, the average total depth of the tissue portion or the skinlayer (e.g., epidermal and dermal layers) is about 1.5 mm. In yet otherembodiments, the average total depth of the tissue portion or the skinlayer (e.g., epidermal and dermal layers) is about 3 mm. In otherembodiments, the average total depth of the tissue portion or the skinlayer (e.g., epidermal and dermal layers) is about 6 mm. In furtherembodiments, the tissue portion does not include a significant amount ofsubcutaneous tissue, and any apparatus described herein can be optimized(e.g., with one or more stop arrangements) to control the depth of theablation and/or the length of the ablated tissue portions.

Such components for making ablations (e.g., drills, blades and/or tubes)can include one or more stop arrangements (e.g., one or more collars,which can be coupled to the blade to allow for adjustment along the longaxis of the blade or which can be coupled to the outer portion of thetube and be adjusted along the long axis of the tube to control thedepth of ablation in the biological tissue); one or more sleeves arounda portion of a blade and/or a tube, such that the sleeve is slidablytranslatable along the longitudinal axis of the tube or blade (e.g., toablate tissue portions below the surface of the skin region); avibrating arrangement (e.g., a piezoelectric element, a solenoid, apneumatic element, or a hydraulic element) that mechanically couples toat least one blade or hollow tube (e.g., to promote insertion of one ormore blades or tubes into the skin region, such as by providing anamplitude of vibration in the range of about 50-500 μm (e.g., betweenabout 100-200 μm) or by providing a frequency of the induced vibrationsto be between about 10 Hz and about 10 kHz (e.g., between about 500 Hzand about 2 kHz, or even about 1 kHz)); a suction or pressure system(e.g., by squeezing a flexible bulb or deformable membrane attachedthereto or by opening a valve leading from a source of elevatedpressure, such as a small pump) to stabilize the surrounding skin regionprior to ablation and/or to facilitate removal of the skin portions fromthe tube; a pin within the lumen to the tube to facilitate removal ofthe skin portions from the tube; one or more actuators for positioning,translating, and/or rotating the one or more blades and/or tubesrelative to the skin portion or relative to the optional one or morepins; a housing or frame to stabilize the surrounding skin region priorto ablation; one or more actuators for positioning and/or translatingthe one or more pins relative to the skin portion or relative to one ormore tubes; one or more sensors (e.g., force sensors, optical sensors,laser fibers, photodetectors, and/or position sensors) in communicationwith one or more tubes, blades, pins, actuators, valves, or pressuresystems to detect the position of the tubes or pins, the presence of atissue portion in the tube, the position of the apparatus relative tothe treated skin portion; a reciprocating arrangement attached to a baseor a substrate having one or more attached blades or tubes (e.g., amotor or actuator configured to repeatedly insert and/or withdrawn oneor more blades or tubes); a fluid system coupled to the blades and/ortubes to facilitate removal of ablated tissue portions or to irrigatethe skin portion, e.g., with saline or a phosphate buffered solution; aheat source (e.g., a resistive heater or current) in communication withthe blade and/or tube to promote cauterization of ablation of tissueportions; an optical element (e.g., a lens, a prism, a reflector, etc.)to facilitate viewing of the skin portion beneath the apparatus, tube,or blade; and/or an abrading element optionally mounted on a rotatingshaft (e.g., to promote dermabrasion).

EXAMPLES Example 1 Drill Apparatus for Forming an Ablated Tissue Portion

An ablated tissue portion for the treatment of skin can be formed bymechanical means. For example, a drill equipped with a depth stop, adrill bit configured to remove tissue and having a diameter less than 1mm, can be used to form an ablated tissue portion (FIG. 1). The drill ispositioned over the skin region to be ablated. The drill bit is rotatedusing the drill motor to a rotational speed sufficient for the drill bitto incise the tissue (e.g., a drill rotational speed between about 50 to2500 rpm, such as about 500 rpm or any ranges described herein). As thedrill bit enters the tissue, the device is moved in the Z directionuntil the depth stop makes contact with the skin surface. The drill bitrotation can be reversed to remove the drill bit and complete theablation to form an ablated tissue portion.

Many drill bit designs and materials can be used in the exemplary deviceand method. For example, a twist bit can be used to form a cylindricalshaped hole with uniform sides. A paper drill can be used to form largerdiameter hole. A spoon bit (FIGS. 2A and 2B) can be used to make roundedbottom hole or ablated tissue portion. A microauger or tube with cuttingteeth can be rotated using a drill to ablate tissue to form an ablatedtissue portion. Drill bits can be made of a many materials including:steel, stainless steel, metals, metal alloys (e.g., surgical steel),cobalt steel alloys, metal carbides, polycrystalline diamond, plastic,and ceramics. Drill bits can be made from composite materials includingmetals and metal alloys coated with black oxide, titanium nitride,titanium aluminum nitride, titanium carbon nitride, diamond powder,zirconium nitride, and other hardening agents and combinations of thematerials herein.

Example 2 Wire or Fiber Apparatus for Forming an Ablated Tissue Portion

The mechanical means for non-thermal ablation of tissue to form anablated tissue portion can be a wire or a fiber attached to a rotatingcomponent. For example, a wire can be attached to a needle such that thewire creates an arc extending from the longitudinal axis of the needle(FIG. 3A). The wire can be attached to the needle adjacent to the needletip and attached in a second location along the needle towards theproximal end of the needle (end attached to rotating component). In thisconfiguration, the tip of the needle anchors itself into the tissue forablation. The rotating component is activated and the wire rotates withthe needle, sweeping out a volume of tissue as the wire turns. Therotational speed can be set to achieve the desired effect (e.g., slowerrotation results in less aggressive ablation of tissue and fasterrotation results in more aggressive ablation of tissue). The shape ofthe hole is dictated by the shape of the wire, thus the wire shown inFIG. 3A ablates a rounded bottomed hole. The needle can be moved intothe skin to increase the depth. The rotating component can be stopped orreversed in order to back out the needle and wire.

In another example, a wire is attached to an axle having the samediameter as the hole to be created. The wire may be attached off-centerand to the outer diameter of the axle. The wire is parallel to the longaxis of the axle. When the axle is rotating at high speed along its longaxis, the wire trajectory defines a cylinder, co-axial with the axle andof same diameter than the axle. The wire is inserted in the skin whilethe axle is rotating and it cuts a cylindrical hole. Removal of cuttissue can be accomplished by the tissue removal apparatuses and methodsdescribed herein.

In another example, a wire containing device can be used to form anablated tissue portion with different diameters along the depth. Forexample, an ablation apparatus can be configured with an axle and a wireattached to the end of the axle (FIG. 3B). In this particularconfiguration, the wire direction can be adjusted from parallel toperpendicular relative to the longitudinal axis of the axle (e.g., thewire can be adjusted by up to 90 degrees). With the wire parallel to thelongitudinal axis, the axle can be rotated at high speed (e.g., 500 to5000 rpm). The hole formed will have a diameter defined by approximatelythe diameter of the axle. The axle and wire can be rotated at high speedand penetrate a skin region to a depth of 4 mm, thus forming a hole of afirst diameter. The axle can be removed and the wire adjusted by 90degrees into a position perpendicular to the longitudinal axis of theaxle. In this configuration, the length of the wire plus the diameter ofthe axle will determine the diameter of the hole formed by the axle andwire. The reconfigured wire and axle (i.e., axle with wire perpendicularto the long axis of the axis) can be rotated at high speed and movedinto the hole previously drilled to a first diameter. The wire and axlecan be moved down the hole to a depth of 2 mm, thus forming a hole witha second diameter. The resulting ablated tissue portion has twodifferent diameters: a first diameter defined by the axle of theablation apparatus and the bottom 2 mm of the hole, and a seconddiameter defined by the sum of the axle diameter and the length of thewire and the top 2 mm of the hole. In some cases, ablated tissueportions with more than one diameter along the depth, in particular alarger diameter at the skin region surface than at the hole depth, canbe more efficiently closed and have improved healing times. Fibers canbe substituted for a wire in any of the above examples of embodiments.

Example 3 Blade Apparatus for Forming an Ablated Tissue Portion

The mechanical means for ablation may include one or more blades. Forexample, an ablation apparatus can be formed by a square shaped tubehaving blades along the bottom edge of each wall of the square tube. Ina further example, an array of square shaped tubes with blade edges(FIG. 4, an array of six square blades) having one or more square tubesseparated by a distance configured to extract about 5-40% of the tissuearea covered by the array (e.g., the sum of the area of all the squaretubes is 5-40% of the total area covered by the array). The blades arepushed into the skin in the direction indicated by the arrow. Differenthole patterns may be cut depending on the geometry and number of blades(e.g., a triangle, hexagon, or octagon). Blades may be inserted into thetissues with sufficient force and speed to produce a desired effect. Thehole depth can be controlled by the depth of the blade or a stop featureon the apparatus or device.

Example 4 High Pressure Fluid Jet Apparatus for Forming an AblatedTissue Portion

Non-thermal ablation of tissue can be achieved using high pressure fluidjets (e.g., fluid under pressures greater than about 1380 kPa or 200psi, including up to 100000 psi). Optionally, operating pressure may belowered by adding an abrasive (e.g., micro-particles) in the fluid(e.g., water). For example, a fluid stream can be contained in acylindrical body under high pressure. Fluid jets are formed by holes inthe cylindrical body. The cylindrical body and fluid jets can be locatedexternal to and with the fluid jets being directed at the skin surface(FIG. 5A). The fluid jets ablate tissue without thermal energy beingtransferred to the surrounding tissue. The fluid can be removed with avacuum apparatus or similar means. In another embodiment, the jet arraycan be moved (e.g., in a circular fashion) in relation to the skin so asto produce an array of cylindrical ablations.

In another example, a cylindrical body containing a plurality of fluidjets that can be inserted in the fatty layer, under the dermis andepidermis (FIG. 5B). The array of fluid jets emits fluid at very highpressure and ablates tissue. A suction tube can be used to remove thefluid and debris. Alternatively, a low pressure out-flow tube can bepositioned on the surface of the skin collecting fluid and debris (FIG.5B). The high pressure fluid jet flow can be continuous or discontinuousfluid flow. Discontinuous fluid flow can provide a step to remove offluid and debris prior to re-activating the high-pressure jet.

Example 5 Cryosurgery Apparatus for Forming an Ablated Tissue Portion

Non-thermal ablation can be achieved using cryosurgical apparatuses andmethods. For example, an array of miniature cold probes mounted on asupport structure can be applied to a skin surface (FIG. 6A). The probeslocally decrease the skin temperature, freeze and destroy the tissue.

In another example, an array of miniature cold needles mounted in asupport structure can be inserted into the skin (FIG. 6B). The needlescan be made of a thermal conductive material (e.g., a metal). A longerneedle can destroy deeper skin structures. The penetrating componentscan be temperature controlled (in contact with a heat sink ortemperature control system).

In another example, penetrating components can have regions composed oftemperature non-conductive (e.g., thermal insulator) materials to helpshield specific regions or depths of the tissue from exposure toextremes of temperature of the cold needle. For example, a cold needlecan be used with a layer of insulating material forming a spiral patternalong the length of the needle. In this manner, holes with manydiameters and surface geometries (e.g., a spiral pattern) can be formed.

Example 6 Chemical Agent Apparatus for Forming an Ablated Tissue Portion

Ablated tissue portions can be formed using chemical agents distributedin a skin region by a penetrating component. For example, an array ofneedles containing holes can be introduced in a skin region (FIG. 7).The needle side holes can inject a chemical denaturizing agent atmultiple depths, thus ablating regions of skin tissue. In anotherexample, the needle can have holes spaced such that the chemical agentis not distributed along the entire length of the needle. In thisconfiguration, ablation can occur at specific locations along the lengthof the needle, thus creating ablated tissue portions with differentdiameters along the depth or holes with serrated edges.

Example 7 Electroporation Apparatus for Forming an Ablated TissuePortion

Ablated tissue portions can be formed by the irreversibleelectroporation of tissue. An array of conductive needles, arranged aspairs of needles, can inserted into the skin (FIG. 8). The needles canbe connected to a generator that emits pulses of electricity of apre-selected duration, frequency and intensity. The needle array can beconfigured to have an equal number of active electrodes and returnelectrodes located in close proximity as to generate a pulsed and highintensity electrical field between pairs of electrodes (e.g., bipolarelectrode pair). Once activated, an electrical field leads tonon-thermal, irreversible electroporation of the tissue located betweenelectrode pairs. The treatment parameters can be selected as to onlygenerate apoptosis of skin cells. The shape of the ablated tissueportion is determined by the geometry of the area between the twoneedles or electrodes. For example, the two needles can be placed atdifferent angles relative to each other (as opposed to parallel as shownin FIG. 8), thus creating a hole with non-parallel sides. In anotherexample, the penetrating components can be different or complimentaryshapes to provide ablated tissue portions with serrated edges and otherstructures.

In another example, a bipolar needle electrode having an active and areturn electrode on a cylindrical body, separated by an electricallyinsulating material can be used in place of a pair of needles (FIG. 9).Activation of the electrode causes ablation around the cylindrical bodyas energy moves from the active electrode through the skin to the returnelectrode. The electrode can have many shapes, thus forming ablatedtissue portions with different geometries.

Example 8 Tissue Removal Apparatus Using Physical or Mechanical Means

Following ablation, tissue and debris can be removed by physical ormechanical means. For example, a removal device can be configured with aflexible support layer attached to an adhesive layer (e.g., tape). Thisdevice can be applied on the skin following ablation (FIG. 10A). Theadhesive layer attaches to the tissue to be removed as well as to theremaining skin surface. When the device is lifted from the skin, thetissue to be removed (e.g., ablated tissue portion) is pulled out of theholes. In another example, an array of probes can be applied on thetissue to be removed (FIG. 10B). The probe can be a rigid cylinder inwhich the bottom surface is covered with an adhesive. Alternatively, theprobe can be a probe in which the bottom surface is temperaturecontrolled and sticks to the skin due to freezing between the probe andskin region surfaces. The probes used for tissue removal may be combinedwith the ablation apparatuses discussed herein.

Example 9 Tissue Removal Apparatus Using Thermal Energy

A mechanical ablation apparatus can be used to isolate a tissue regionprior to removal of the circumscribed tissue by a thermal ablationmethod. By isolating the tissue portion to be removed (e.g., ablatedtissue portion) from the surrounding tissue, a thermal ablation methodcan be used without inducing coagulation in the surrounding (e.g.,non-ablated) tissues. For example, a micro-coring component (e.g.micro-coring needles, micro-coring paper drill, micro-coring hole saw ormicro-coring blade assembly) may be inserted in the skin to cut thetissue without generation of thermal injury. While the micro-coringcomponent is still in the skin, an ablative laser (e.g., a laserdelivered by a light guide inside the micro-coring needle) may be usedto vaporize the tissue contained in the micro-coring member (FIG. 12).The micro-coring component material may be chosen as to act as a thermalinsulator to prevent heating of the tissue outside of the micro-coringcomponent. In one non-limiting embodiment, thermal ablation can beperformed first followed by coring to remove the coagulation zone.

Example 10 Tissue Positioning Apparatuses

A tissue positioning apparatus can provide a flat skin surface fornon-thermal ablation or skin removal. Tensioning rods (FIG. 13) can beused to apply a force to the skin surface by moving the rods away fromeach other, thus providing a flat skin region in between. For example,two rubber rods can be positioned adjacent to one another on a skinregion. The rods can be moved apart while a force is applied on the rodsto provide tension on the skin region (e.g., a downward force of greaterthan about 10 N/mm²). The tension force can be maintained duringablation and/or tissue removal. In some embodiments, tensioning rods canalso be used to apply a force to the skin surface by moving the rodstoward each other, thus pinching the skin to elevate the dermis awayfrom the underlying structures (e.g., sub-dermal muscle layer, bloodvessels, and nerve fibers) (FIG. 22).

A skin region can be held flat by a series of micro-hooks (FIG. 14) ormicro-barbs. For example, four metal, multiprong tabs can be placed inthe four corners of a skin region under tension. The pronged tabsmaintain the tension force and hold the skin region between the prongsflat during ablation and/or tissue removal.

Needles that provide a gripping force (“needle grippers”) can bedeployed in the dermis layer to lift the skin and elevate the dermisaway from the underlying structures (e.g., sub-dermal muscle layer,blood vessels, and nerve fibers). Once inserted in the skin (FIG. 23,arrow 1), opposite needles can be pulled away (FIG. 23, arrow 2) fromeach other to generate skin tension. The needles can then be pulled awayfrom the skin surface to create a displacement of the dermis away fromthe underlying structures to prevent injury to muscle, blood vessels,and nerve fibers by the micro-coring needles. The level of skin tensioncan be adjusted by pulling opposite needles away from each other in onedirection to create a uni-directional skin tension. The needles can beretracted to release the skin.

A vacuum can be applied to a tissue surface to provide a flat skinregion (FIG. 15). For example, a housing (e.g., a vacuum tube) with anareal dimension of 10 cm², access ports for an array of ablationapparatuses, and attached to a vacuum source can be brought into contactwith a skin region under tension. A vacuum of 101.3 kPa is applied tothe housing, thus forming a seal between the skin region and thehousing. The skin region sealed within the housing is held flat andunder tension by the reduced pressure. An array of ablation apparatusescan be moved into the housing using the access ports. The tissue of theskin region within the housing can be ablated while the housing remainsunder a vacuum. In one non-limiting embodiment, the needles can alsoconvey the vacuum.

A tissue positioning apparatus having a cold surface and a series ofchannels configured to accept an array of ablation apparatuses can beused to position a skin region by freezing the skin to the cold surface(FIG. 16). For example, a housing containing a temperature controlledsurface and access ports can be cooled to 0 degrees Celsius. The coldsurface is brought in contact with a skin region under tension. The coldsurface joins with the skin region once freezing occurs between the twosurfaces. An array of ablation apparatuses can be moved through theaccess ports and used to ablate the tissue of the skin region.

A tissue positioning apparatus having an adhesive surface and a seriesof channels configured to accept an array of ablation apparatuses can beused to position skin by adhering the skin to the adhesive surface (FIG.17). For example, a housing containing an adhesive covered surface andaccess ports can be brought in contact with a skin region under tension.The adhesive surface joins with the skin region, thus maintaining thetension and providing a flat skin region. An array of ablationapparatuses can be moved through the access ports and used to ablate thetissue of the skin region. In another embodiment, the ablation device,e.g., a needle or row of needles, inserts into the tissue and then moveslaterally, creating tension on the skin, before the next row of needlesinserts into the skin. As part of the same mechanism, the skin might beheld back by a tension roller (e.g., as provided in FIG. 13).

Example 11 Duration of the Mechanical Fractional Ablation Procedure

The apparatuses, devices, and procedures of the invention can beoptimized to perform an ablation procedure within a particular timeframe. The following theoretical calculations are non-limiting andprovided as an example only. In this non-limiting example, thetheoretical calculation involves tightening the skin of the face. Thecalculation methodology is based on the following approximation: asurgical facelift procedure requires ablation of a tissue surface thatcould also be ablated by mechanical fractional ablation. Mechanicalfractional ablation can involve, e.g., tissue coring by a micro-needlearray, such as any described herein. The number of micro-coring eventsrequired to remove a tissue surface equivalent to a face-lift iscalculated. The number of events is then multiplied by the duration ofone micro-coring event to evaluate the duration of the ablationprocedure.

Tightening of the tissue of the face is provided as an illustration forthis theoretical analysis. This example may be relevant for otherprocedures, such as for determining the duration of other procedures(e.g., a brow lift, forehead lift, and/or blepharoplasty). Typicalplacement of incisions for a facelift include those beginning in thehairline at the temples, curving in front of the ear and then around thebottom of the ear, and generally ending near the hairline on the back ofthe neck. This incision is made on both sides of the head. Without beinglimited by this example, the length of the incision is generally about250 mm. The skin is pulled towards the back of the head. A band of skinis excised; its width can be estimated to be less than about 5 mm.Therefore, the total skin surface removed is given by the followingequation:

Skin removed=2×250 mm×5 mm=2500 mm²

Mechanical ablation can be achieved by any useful method, such as anydescribed herein. For example, Fernandes et al. demonstrated mechanicalfractional ablation with 23G and 25G coring needles in a pig model(Fernandes et al., Micro-mechanical fractional skin rejuvenation, PlastReconstr Surg. 2013 February; 131(2):216-23, which is herebyincorporated by reference in its entirety). Up to 40% of the tissue wasremoved in the treatment area, and the skin healed without visiblescars. A coring needle can be used to remove a cylindrical volume oftissue which diameter is determined by the inner diameter of the needle,as well as the insertion depth of the needle in the skin. Thus, 23G and25G needles remove tissue cylinders of about 337 μm and 260 μm indiameter, respectively. Fernandes et al. confirmed experimentally thatthe coring sites were about 300 μm in diameter. In another example,fractional lasers are broadly used clinically to rejuvenate the skin.They produce lesions that have similar dimensions to the micro-coringlesions described above. For example, Bedi et al. showed that a Fraxelsystem generates lesions of about 200 μm in diameter (Bedi et al., Theeffects of pulse energy variations on the dimensions of microscopicthermal treatment zones in nonablative fractional resurfacing, LasersSurg Med. 2007 February; 39(2):145-55, which is hereby incorporated byreference in its entirety).

For our calculation, we assume that the device uses 25G needles andgenerates lesions of similar size to fractional lasers. Using thisassumption, the surface of tissue removed by a single 25G needle is:

$\frac{\pi \; d^{2}}{4} = {\frac{\pi \; 0.26^{2}}{4} = {0.05\mspace{14mu} {mm}^{2}}}$

In particular non-limiting embodiments, multiple coring needles areassembled in an array to expedite the procedure. There is robustevidence that multiple needles can penetrate the skin simultaneouslywhile avoiding a “needle-bed” effect that would preclude penetration ofthe needles in the tissue. For instance, Fernandes et al. assembled 4needles with a 8 mm separation in a piece of rubber for their animalstudy. In another example, the Dermaroller® is a micro-needling devicecurrently used in clinical practice (Majid, Microneedling therapy inatrophic facial scars: an objective assessment, J Cutan Aesthet Surg.2009 January; 2(1):26-30). The Dermaroller® needles are non-coring,conic-tip needles that are up to 1.5 mm in length and about 250 μm indiameter. In general, two rows of 8 needles are assembled on a flatplastic holder with a 1.5 mm spacing, and a minimum of 16 needlespenetrate the skin simultaneously. In yet another example, the Dermapen®is another micro-needling device with non-coring, conic tip needles. TheDermapen® uses eleven 32G needles penetrating the skin up to 2.5 mm indepth. An electro-mechanical actuator pushes the 11 needles in thetissue at elevated frequency, allowing very fast treatment of a largearea of the body. The manufacturer claims that the Dermapen® mechanismallows up to 1000 holes per second. In particular embodiment, thedevices, apparatuses, and methods of the invention include 1, 2, 3, 4,5, 6, 7, 8, 9, or 10 skin-penetrating component(s) (e.g., a needle, adrill, a microauger, a tube comprising cutting teeth, a spoon bit, awire, a fiber, a blade, a high-pressure fluid jet, a cryoprobe, acryoneedle, a multi-hole needle comprising one or more chemical agents,a microelectrode, and/or a vacuum, or any other component describedherein) that can penetrate the skin simultaneously.

Further examples of treatment areas and surface of tissue removed by asingle skin-penetrating component are provided herein, e.g., Table 1. Inaddition, any beneficial areal fraction of the skin region can beremoved, such as an areal fraction of less than about 70% (e.g., asdescribed herein). Based on the above-described equations, a skilledartisan would be able to calculate the number of holes or ablated tissueportions within the treatment area or areal fraction of the treatmentarea. The following paragraphs provide guidance on how the devices,apparatuses, or methods can be optimized for a particular treatment timeor duration.

The speed of the skin-penetrating component can be optimized fortreating skin. In some embodiments, the speed is similar to that of abiopsy gun (e.g., the HS Multi 22 device from BIP/Bard for harvest softtissue clinically, see Konermann et al., Ultrasonographically guidedneedle biopsy of benign and malignant soft tissue and bone tumors, JUltrasound Med. 2000 July; 19(7):465-71), such as about 30 m/s. Assumingthis speed and that the thickness of the epidermal and dermal layer is 3mm in the human face (Kakasheva-Mazhenkovska et al., Variations of thehistomorphological characteristics of human skin of different bodyregions in subjects of different age, Prilozi. 2011 December;32(2):119-28), the ablation of the tissue at a speed of 30 m/s takes (3mm/30,000 mm/s)=0.1 ms. In some embodiments, the speed of theskin-penetrating component (e.g., any described herein) is 100 timesslower than the biopsy gun, such that the total time required for oneactuation is about 10 ms. In particular embodiments, the speed of theskin-penetrating component is about 50 m/s, 40 m/s, 30 m/s, 20 m/s, 10m/s, 5 m/s, 1 m/s, 0.9 m/s, 0.8 m/s, 0.7 m/s, 0.6 m/s, 0.5 m/s, 0.4 m/s,0.3 m/s, 0.2 m/s, or 0.1 m/s. In other embodiments, the total time for asingle actuation accounts for the travel of the skin-penetratingcomponent(s) back to the starting position and/or for the collection ofthe tissue sample in the skin-penetrating component (e.g., via a vacuumsystem). In particular embodiments, the time for a single actuation isabout 100 ms, 90 ms, 80 ms, 75 ms, 60 ms, 50 ms, 40 ms, 30 ms, 20 ms, 10ms, 9 ms, 8 ms, 7 ms, 5 ms, 5 ms, 1 ms, 0.9 ms, 0.8 ms, 0.7 ms, 0.6 ms,0.5 ms, 0.4 ms, 0.3 ms, 0.2 ms, or 0.1 ms.

The time required to remove the total tissue surface is given by thefollowing formula:

$\frac{{surface}\mspace{14mu} {to}\mspace{14mu} {be}\mspace{14mu} {removed}}{\begin{matrix}{{surface}\mspace{14mu} {removed}\mspace{14mu} {by}\mspace{14mu} 1\mspace{14mu} {component} \times} \\{{number}\mspace{14mu} {of}\mspace{14mu} {{component}(s)}\mspace{14mu} {per}\mspace{14mu} {array}}\end{matrix}} \times {component}\mspace{14mu} {actuation}\mspace{14mu} {{time}.}$

The component can be a skin-penetrating component. With the assumptionsdescribed in the previous paragraph, the ablation duration can becalculated as follows:

${\frac{2500\mspace{14mu} {mm}^{2}\mspace{14mu} {to}\mspace{14mu} {be}\mspace{14mu} {removed}}{0.05\mspace{11mu} {mm}^{2} \times 10\mspace{14mu} {{component}(s)}\mspace{14mu} {per}\mspace{14mu} {array}} \times 0.01\mspace{14mu} {ms}} = {50\mspace{14mu} {s.}}$

Assuming that the system is firing at high frequency (e.g., about 100times per second), the user (e.g., a physician) can move the device orapparatus across the face continuously and slowly while firing oractuating the device. This continuous firing mechanism may or may not beincorporated into the device or apparatus.

Accordingly, the present example provides an exemplary, simple formulafor calculating tissue ablation. This calculation is based on the totalskin surface to be removed, the geometry of the ablation systemdetermined by experimental data on mechanical micro-coring and by thedesign of existing micro-needling devices, and the speed of theactuation mechanism determined by the performance of comparable biopsysystems. This calculation can be altered by a skilled artisan foroptimal treatment and/or effect. With the above-described assumptions,tissue ablation can last about 1 minute. The total duration of theprocedure can also account for other steps, such as for the preparationof the skin (e.g., for cleaning and/or applying a local anesthetic)and/or application of compression wound dressing after tissue ablation.Including additional steps, the total procedure duration could be about½ hour, and tissue ablation represents an insignificant fraction of thetotal procedure time. This estimated, non-limiting example of totalprocedure time is comparable to existing non-invasive skin resurfacingprocedures, such as fractional laser treatment.

Example 12 Swine Skin Healing Progression after Treatment withMicro-Coring Needles

The methods of the present invention were carried out in an animal modelof skin resurfacing, and the progression of skin healing followingablation treatment was followed by staining biopsied skin samples.Specifically, a Yorkshire pig was treated by a series of ablations witha 19G diameter micro-coring needle and followed up for 90 days aftertreatment. Biopsy samples of the treated skin were taken on days 0, 7,30, 60 and 90. The biopsied tissue was fixed in formalin, sliced,stained (Masson's trichrome stain), and photographed. FIG. 20 shows thishealing progression after treatment. The full dermis is shown andsub-dermal fat can easily be seen on some of the photographs. Treatmentsites were readily identified at Day 0, at which time cored regions werecharacterized by linear defects, sometimes containing blood, fibrin,and/or few inflammatory cells, extending from the skin surface throughthe dermis. These cored regions were progressively filled in byfibroproliferative tissue which exhibited maturation across subsequenttime points. At Day 7, fibroproliferative tissue filled treatmenttracts. The fibroproliferative tissue appeared moderately cellular andimmature, sometimes with small amounts of remaining fibrin. At Day 30,treatment sites were indistinct from surrounding tissue, containing lowcellularity, moderately dense collagen, and few capillaries withinflammatory cells, and normal epidermis was observed. The histologicappearance of treatment sites at Day 60 was similar to surroundingtissue. Normal epidermis was observed at Day 60. At Day 90, treatmentsites were identifiable but very indistinct from surrounding tissue. Thereparative fibrous tissue at treatment sites lacked the normalpre-treatment dermal architecture of thick and interwoven collagenbundles and elastic fibers. Instead, fibrous tissue at treatment sitesconsisted of denser sheets of thin collagen fibers lacking elasticfibers. Few capillaries permeated these areas. Inflammation at treatmentsites was negligible to absent. From these results, it appeared thatcomplete skin healing could be achieved within 60 days after treatmentwith micro-coring needles.

Example 13 Treated Abdominal Skin of a Human Subject

A clinical trial was initiated to evaluate the safety and efficacy ofmechanical fractional ablation on the abdominal tissue of healthypatients. Subjects were treated with 19G to 24G diameter needles.Treatment coverage ranged from 5% to 20% of total skin area removed.FIG. 19 shows photographs of the abdominal skin of human subjectstreated with different needle sizes immediately after treatment.Photograph 1 shows a matrix of six treatment zones (two columns, threerows) delimited by tattoo marks. 10% of the skin was removed in each ofthe six treated areas. A different needle gauge was used for eachtreatment area. Needle gauges range from 19G to 24G (see matrix next tothe photograph for allocation of treatment areas to each needle gauge).Photograph 2 is similar to Photograph 1, except 20% of the skin wasremoved in each of the six treated areas. From this stage, a 21 G needlediameter and treatment coverage of 10% were selected as safety thresholdparameters. Selection criteria for the treatment parameters includedabsence of visible scars or other adverse events for up to three monthsafter treatment. FIG. 20 further shows several graphs indicating thechange in linear dimension/surface area of a treated square area(21G/10% or 22G/10%) in comparison with a contra-lateral non-treatedarea of similar dimension (control). The dimension of the treated squareis consistently smaller than the dimension of the control square in adirection orthogonal to Langer lines. The same applies to its surfacearea.

Needles with 21 G diameter were selected to use in the second stage ofthe study. Treatment and control sites were defined within the abdominaltissue area to be removed by the future abdominoplasty procedure. Thesubjects were treated by mechanical fractional ablation after localanesthesia and were evaluated on days 1, 7, 30, 60, and 90post-procedure. FIG. 21 shows the appearance of human abdominal skinbefore and after the skin was treated with 21G diameter micro-coringneedles. The same patch of skin is shown on all four photographs of FIG.21. Photograph 1 was taken before treatment. The presence of tattoomarks delimits the treatment area. Photograph 2 was taken immediatelyafter treatment. The skin was treated with 21G diameter micro-coringneedles. 10% of the total skin surface area was removed. Photograph 3was taken immediately after removal of the compressive wound dressingapplied on the treatment area. Compression was applied in the verticaldirection. Photograph 4 was taken a month after treatment. The treatmentarea is completely healed. Skin compression was achieved by removing 10%of the total skin surface area using 21 G diameter micro-coring needles.The data demonstrate that the treatment is safe, does not generatescars, and results in reduction of the surface area of the treatmentzone in a direction orthogonal to Langer lines.

Further, for mechanical fractional ablation, the extent and persistenceof erythema appeared to correlate with the size of the coring needlesused. No serious adverse effect, either device-related adverse effect orunanticipated adverse effect, has been reported to date. Pain levels of2-4 (on a scale of 0=non pain to 10) were reported on the day oftreatment, 0-2 on day 1 and 7, and dropping to 0 on day 30 andthereafter. None of the subjects patients reported taking painmedications after the procedure. Scarring was not observed withtreatment coverage of 10% and 15% of total skin area removed (FIGS. 19and 21) and with needle diameters of 21 G and smaller.

Other Embodiments

All publications, patent applications, and patents mentioned in thisspecification are herein incorporated by reference.

Various modifications and variations of the described method and systemof the invention will be apparent to those skilled in the art withoutdeparting from the scope and spirit of the invention. Although theinvention has been described in connection with specific desiredembodiments, it should be understood that the invention as claimedshould not be unduly limited to such specific embodiments. Indeed,various modifications of the described modes for carrying out theinvention are intended to be within the scope of the invention.

What is claimed is:
 1. A method of treating skin comprising: (a)positioning said skin using a compressive or a stretching force appliedacross said skin; (b) forming a plurality of ablated tissue portions;and (c) removing said plurality of ablated tissue portions, therebytreating said skin.
 2. The method of claim 1, wherein said plurality ofablated tissue portions have a width to depth ratio of between about1:0.3 to about 1:75.
 3. The method of claim 1 or 2, wherein saidcompressive force applied across said skin compresses said skin in adirection orthogonal to Langer lines.
 4. The method of any one of claims1-3, wherein said plurality of ablated tissue portions is removed usingneedles with 21G.
 5. The method of any one of claims 1-4, wherein saidplurality of ablated tissue portions being removed is about 10% of saidskin within a treatment area.
 6. A method of treating skin comprising:(a) forming a plurality of ablated tissue portions having a width todepth ratio of between about 1:0.3 to about 1:1 or of between about 1:25to about 1:75; and (b) removing said plurality of ablated tissueportions, thereby treating said skin.
 7. A method of treating skincomprising: (a) forming a plurality of ablated tissue portions having achange in width as a function of depth, wherein said change in width isof between about 100 μm to about 500 μm as a function of depth; and (b)removing said plurality of ablated tissue portions, thereby treatingsaid skin.
 8. A method of treating skin comprising: (a) forming aplurality of ablated tissue portions comprising a serratedcross-sectional dimension; and (b) removing said plurality of ablatedtissue portions, thereby treating said skin.
 9. The method of any one ofclaims 1-9, wherein step (b) comprises pulling, squeezing, resorbing,desiccating, or liquefying said plurality of ablated tissue portions.10. The method of any one of claims 6-9, further comprising (c)positioning said skin using a compressive force applied across said skinprior to step (a) and/or (b).
 11. The method of claim 10, wherein step(a) is performed with an ablative apparatus of any one of claims 21-47and/or step (b) is performed with a removal apparatus of any one ofclaims 48-53 and/or step (c) is performed with a positioning apparatusof any one of claims 13-20.
 12. The method of claim 11, wherein saidablative apparatus, said removal apparatus, and said positioningapparatus are configured in a single device.
 13. A positioning apparatusfor positioning skin, said apparatus comprising at least twosufficiently parallel tensioning rods configured to compress skin,wherein said rods are separated by a distance of more than about 0.5 mmand exert a compressing force.
 14. A positioning apparatus forpositioning skin, said apparatus comprising at least two sufficientlyparallel tensioning rods configured to stretch skin, wherein said rodsare separated by a distance of more than about 0.5 mm and exert astretching force.
 15. A positioning apparatus for positioning skin, saidapparatus comprising a plurality of needles configured to grip skin,wherein said needles exert a gripping force.
 16. A positioning apparatusfor positioning skin, said apparatus comprising a plurality ofmicrohooks or microbarbs, wherein each microhook or microbarb isseparated by a distance of more than about 0.5 mm and exerts astretching force.
 17. The positioning apparatus of claim 14 or 16,wherein said separation distance of more than about 1 mm.
 18. Apositioning apparatus for positioning skin, said apparatus comprising avacuum tube having at least one dimension of greater than 1 mm and avacuum source, wherein said vacuum tube is configurably attached to saidsource and exerts a stretching force.
 19. A positioning apparatus forpositioning skin, said apparatus comprising a substrate having at leastone dimension of about 1 mm and a cryosource, wherein said substrate isconfigurably attached to said cryosource and provides a cryotemperatureof about 0 degrees C. or lower.
 20. A positioning apparatus forpositioning skin, said apparatus comprising an adhesive layer having atleast one dimension of about 1 mm.
 21. An ablative apparatus fornon-thermal tissue ablation, said apparatus comprising askin-penetrating component configured to provide an ablated tissueportion having a change in width as a function of depth, wherein saidchange in width is of between about 100 μm to about 500 μm as a functionof depth.
 22. An ablative apparatus for non-thermal tissue ablation,said apparatus comprising a skin-penetrating component configured toprovide an ablated tissue portion comprising a serrated cross-sectionaldimension.
 23. The ablative apparatus of claim 21 or 22, wherein saidskin-penetrating component is configured to provide an ablated tissueportion having a width to depth ratio of between about 1:0.3 to about1:75.
 24. An ablative apparatus for non-thermal tissue ablation, saidapparatus comprising a skin-penetrating component configured to providean ablated tissue portion having a width to depth ratio of between about1:0.3 to about 1:1 or of between about 1:25 to about 1:75.
 25. Theablative apparatus of any one of claims 21-23, wherein saidskin-penetrating component comprises a drill, a microauger, a tubecomprising cutting teeth, a spoon bit, a wire, a fiber, a blade, ahigh-pressure fluid jet, a cryoprobe, a cryoneedle, an ultrasoundneedle, a multi-hole needle comprising one or more chemical agents, amicroelectrode, and/or a vacuum.
 26. The ablative apparatus of any oneof claims 21-24, further comprising one or more components, wherein saidcomponents produce a mechanical force.
 27. The ablative apparatus ofclaim 26, wherein said components are selected from the group consistingof a motor, an axle, an adjustable depth stop, an in-flow tube, a returnelectrode, a generator, and an electrical insulator.
 28. The ablativeapparatus of any one of claims 21-27, further comprising a plurality ofsaid skin-penetrating components in an array.
 29. An ablative apparatusfor non-thermal tissue ablation, said apparatus comprising: a. askin-penetrating component comprising a drill bit comprising one or morespiral channels, a microauger comprising a spiral flange, a hollow drillbit, a tube comprising cutting teeth, and/or a spoon bit; and b. a motorconfigured to rotate said component, wherein said motor is configurablyattached to said component.
 30. An ablative apparatus for non-thermaltissue ablation, said apparatus comprising: a. a skin-penetratingcomponent comprising a wire and/or a fiber having a first attachmentpoint and a second attachment point; b. an axle having a sharpeneddistal end, a center portion, and a proximal end, wherein said firstattachment point of said component is configurably attached to saiddistal end of said axle; and c. a motor configured to rotate saidcomponent, wherein said motor is configurably attached to said proximalend of said axle.
 31. The ablative apparatus of claim 30, wherein saidskin-penetrating component further comprises a second attachment pointand said second attachment point of said component is configurablyattached to said center portion of said axle.
 32. An ablative apparatusfor non-thermal tissue ablation, said apparatus comprising askin-penetrating component comprising a plurality of cylindrical bladesor a plurality of straight blades assembled in a fractional pattern. 33.The ablative apparatus of claim 32, wherein at least one of saidplurality of cylindrical blades is configurably attached to an actuatorfor pushing the blade into the skin.
 34. The ablative apparatus of claim33, wherein said actuator is a vibrating mechanism.
 35. An ablativeapparatus for non-thermal tissue ablation, said apparatus comprising: a.a skin-penetrating component comprising a high pressure fluid jet; b. anin-flow tube configured to deliver one or more fluids to be emitted fromsaid fluid jet; and c. an optional out-flow tube configured to collectsaid one or more fluids after being emitted from said fluid jet.
 36. Anablative apparatus for non-thermal tissue ablation, said apparatuscomprising: a. a skin-penetrating component comprising one or morecryoprobes and/or one or more cryoneedles; b. a cryosource, wherein eachcryoprobe and/or cryoneedle is configurably attached to said cryosourceto provide cryotemperature treatment to skin; and c. an optionalinsulator portion to shield regions of non-treated skin from exposure tosaid cryotemperature treatment, wherein said insulator portion isconfigurably attached to said component.
 37. The ablative apparatus ofclaim 36, wherein said skin-penetrating component comprising two or morecryoprobes and/or one or more cryoneedles.
 38. An ablative apparatus fornon-thermal tissue ablation, said apparatus comprising: (a) askin-penetrating component comprising one or more needles, wherein eachneedle comprises a plurality of holes configured to deliver one or morechemical or bioactive agents to skin; and (b) a depot comprising saidone or more chemical or bioactive agents, wherein each needle isconfigurably attached to said depot for delivering said one or morechemical or bioactive agents.
 39. The ablative apparatus of claim 38,wherein said skin-penetrating component comprising two or more needles.40. An ablative apparatus for non-thermal tissue ablation, saidapparatus comprising: (a) a skin-penetrating component comprising one ormore microelectrodes, wherein each microelectrode comprises an activeelectrode and a return electrode, or comprising a femtosecond laser; (b)a generator configurably attached to each of said microelectrodes orlaser; and (c) an optional electrical insulator portion to shieldregions of non-treated skin from exposure to electrical and/or thermalenergy, wherein said electrical insulator portion is configurablyattached to said component.
 41. The ablative apparatus of claim 40,wherein said skin-penetrating component comprising two or moremicroelectrodes.
 42. An ablative apparatus for non-thermal tissueablation, said apparatus comprising: (a) a skin-penetrating componentcomprising one or more needles, wherein each needle comprises aplurality of holes configured to deliver vacuum to skin; and (b) avacuum source, wherein each needle is configurably attached to saidsource.
 43. The ablative apparatus of claim 42, wherein saidskin-penetrating component comprises two or more needles.
 44. Theablative apparatus of claim 42 or 43, wherein said vacuum sourcecomprises an absolute pressure less than about 6.3 kPa.
 45. The ablativeapparatus of any one of claims 21-44, wherein said apparatus isconfigured to provide from about 10 to about 10000 ablated tissueportions per cm² area of the skin region.
 46. The ablative apparatus ofany one of claims 21-45, wherein said needles comprise needles with 21G.47. The ablative apparatus of any one of claims 21-46, wherein saidablative apparatus removes about 10% of skin within a treatment area.48. A removal apparatus for removing one or more ablated tissueportion(s), said apparatus comprising: (a) a substrate comprising aplurality of holes; and (b) a vacuum source, wherein said substrate isconfigurably attached to said source to deliver vacuum through each holeand to each of said one or more ablated tissue portion(s).
 49. A removalapparatus for removing one or more ablated tissue portion(s), saidapparatus comprising an adhesive layer or an array of probes configuredto contact each of said one or more ablated tissue portion(s).
 50. Aremoval apparatus for removing one or more ablated tissue portion(s),said apparatus comprising: (a) one or more needles configured to contacteach of said one or more ablated tissue portion(s); and (b) a heatsource configured to deliver heat through the lumen of each needle andto each of said one or more ablated tissue portion(s).
 51. The removalapparatus of claim 50, wherein said apparatus comprises two or moreneedles.
 52. The removal apparatus of claim 50 or 51, wherein said heatsource is selected from the group consisting of a laser source, a hotneedle, radiofrequency, ultrasound, a heated gas, or a heated liquid.53. A removal apparatus for removing one or more ablated tissueportion(s), said apparatus comprising: (a) a wire having a firstattachment point and a second attachment point; (b) an axle having asharpened distal end, a center portion, and a proximal end, wherein saidfirst attachment point of said wire is configurably attached to saiddistal end of said axle and said second attachment point of said wire isconfigurably attached to said center portion of said axle, and whereinsaid axle is configured to contact each of said one or more ablatedtissue portion(s); (c) a motor configured to rotate said wire, whereinsaid motor is configurably attached to said proximal end of said axle;(d) a vacuum source, and (e) a substrate comprising a plurality ofholes, wherein said substrate is configurably attached to a vacuumsource to deliver vacuum through each hole and to each of said one ormore ablated tissue portion(s).
 54. A device comprising: (a) an ablativeapparatus for non-thermal tissue ablation of any one of claims 21-47;and (b) a removal apparatus for removing one or more ablated tissueportion(s) of any one of claims 48-53, wherein said removal apparatus isconfigured to remove one or more ablated tissue portion(s) ablated withsaid ablative apparatus.
 55. The device of claim 54, wherein said devicecomprises: (a) the ablative apparatus of claim 23 and the removalapparatus of any one of claim 48, 49, or 50; (b) the ablative apparatusof claim 21 and the removal apparatus of any one of claim 48, 49, or 50;(c) the ablative apparatus of claim 22 and the removal apparatus of anyone of claim 48, 49, or 50; (d) the ablative apparatus of claim 29 andthe removal apparatus of any one of claim 48, 49, or 50; (e) theablative apparatus of 30 and the removal apparatus of claim 48, 49; or(f) the ablative apparatus of 32 and the removal apparatus of any one ofclaims 48,
 49. 56. The device of claim 54, further comprising: apositioning apparatus for positioning skin of any one of claims 13-20,wherein said positioning apparatus is configured to position skin priorto ablation with said ablative apparatus and/or prior to removal withsaid removal apparatus.
 57. The device of claim 54 or 56, furthercomprising one or more sensors to detect position, temperature, skinproximity, skin contact, and/or changes in inductive coupling.
 58. A kitcomprising: (a) an ablative apparatus for non-thermal tissue ablation ofany one of claims 21-47; and (b) a removal apparatus for removing one ormore ablated tissue portion(s) of any one of claims 48-53.
 59. The kitof claim 58, wherein said removal apparatus comprises a pin, anadhesive, a probe array, a vacuum, a compression element, a lasersource, a high-pressure fluid jet, a cryoprobe, a cryosource, acryoneedle, a multi-hole needle comprising one or more chemical orbioactive agents, a microelectrode, a wire, and/or a fiber.
 60. The kitof claim 58 or 59, further comprising a positioning apparatus forpositioning skin of any one of claims 13-20.
 61. The kit of claim 60,wherein said positioning apparatus comprises a tension rod, a microhook,a microbarb, vacuum, a cryoprobe, a cryosource, an adhesive, a switch,and/or a sensor.
 62. A method of treating skin comprising (a) forming aplurality of ablated tissue portions using a 21 G needle; and (b)removing said plurality of ablated tissue portions, wherein 10% of saidskin within a treatment area is removed.
 63. The method of claim 62,wherein said plurality of ablated tissue portions are removed with amultiple needle array.
 64. The method of claim 62, wherein said treatingresults in a reduction of skin surface area.
 65. The method of claim 64,wherein said reduction in skin surface area occurs in a directionorthogonal to Langer lines.